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1.
Nature ; 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38599239

RESUMEN

Gasdermin D (GSDMD) is the common effector for cytokine secretion and pyroptosis downstream of inflammasome activation and was previously shown to form large transmembrane pores upon cleavage by inflammatory caspases to generate the GSDMD N-terminal domain (GSDMD-NT)1-10. Here we report that GSDMD Cys191 is S-palmitoylated and palmitoylation is required for pore formation. S-palmitoylation, which does not affect GSDMD cleavage, is augmented by mitochondria-generated reactive oxygen species (ROS). Surprisingly, cleavage-deficient D275A GSDMD is also palmitoylated after inflammasome stimulation or treatment with ROS activators, and causes pyroptosis, although less efficiently than palmitoylated GSDMD-NT. Palmitoylated, but not unpalmitoylated, full-length GSDMD induces liposome leakage, and forms a pore similar in structure to GSDMD-NT pores shown by cryogenic electron microscopy. zDHHC5 and zDHHC9 are the major palmitoyltransferases that mediate GSDMD palmitoylation, and their expression is upregulated by inflammasome activation and ROS. The other human gasdermins are also palmitoylated in their N-termini. These data challenge the concept that cleavage is the only trigger for GSDMD activation. They suggest that reversible palmitoylation is a checkpoint for pore formation by both GSDMD-NT and intact GSDMD that serves as a general switch for the activation of this pore-forming family.

2.
Science ; 381(6657): 569-576, 2023 08 04.
Artículo en Inglés | MEDLINE | ID: mdl-37535730

RESUMEN

Common γ chain (γc) cytokine receptors, including interleukin-2 (IL-2), IL-4, IL-7, IL-9, IL-15, and IL-21 receptors, are activated upon engagement with a common γc receptor (CD132) by concomitant binding of their ectodomains to an interleukin. In this work, we find that direct interactions between the transmembrane domains (TMDs) of both the γc and the interleukin receptors (ILRs) are also required for receptor activation. Moreover, the same γc TMD can specifically recognize multiple ILR TMDs of diverse sequences within the family. Heterodimer structures of γc TMD bound to IL-7 and IL-9 receptor TMDs-determined in a lipid bilayer-like environment by nuclear magnetic resonance spectroscopy-reveal a conserved knob-into-hole mechanism of recognition that mediates receptor sharing within the membrane. Thus, signaling in the γc receptor family requires specific heterotypic interactions of the TMDs.


Asunto(s)
Subunidad gamma Común de Receptores de Interleucina , Subunidad alfa del Receptor de Interleucina-7 , Dominios y Motivos de Interacción de Proteínas , Subunidad gamma Común de Receptores de Interleucina/química , Subunidad gamma Común de Receptores de Interleucina/genética , Unión Proteica , Transducción de Señal , Resonancia Magnética Nuclear Biomolecular , Subunidad alfa del Receptor de Interleucina-7/química , Subunidad alfa del Receptor de Interleucina-7/genética
3.
Int J Surg ; 109(8): 2414-2426, 2023 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-37161443

RESUMEN

BACKGROUND: Whether there are differences among the new-generation transcatheter aortic valve implantation (TAVI) devices for patients with aortic stenosis remains unclear. The aim of the study was to compare the efficiency and safety of different new-generation TAVI devices for patients with aortic stenosis. MATERIALS AND METHODS: A comprehensive search of PubMed, Embase and Web of Science from their inception to 1 February 2022. Randomized clinical trials and observational studies that compared two or more different TAVI devices were enroled. Pairwise meta-analysis and frequentist network meta-analysis were conducted to pool the outcome estimates of interest. RESULTS: A total of 79 studies were finally included. According to the surface under the cumulative ranking, the top two ranked valves for lower rates of events were as follows: direct flow medical (DFM) (4.6%) and Lotus (48.8%) for lower rate of device success; Sapien 3 (16.8%) and DFM (19.7%) for lower mortality; DFM (8.6%) and Sapien 3 (25.5%) for lower rates of stroke; Evolut (27.6%) and DFM (35.8%) for lower rates of major and life-threatening bleeding; Portico (22.6%) and Sapien 3 (41.9%) for lower rates of acute kidney injury; Acurate (8.6%) and DFM (13.2%) for lower rates of permanent pacemaker implantation; Lotus (0.3%) and Sapien 3 (22.7%) for lower rates of paravalvular leak; Evolut (1.4%) and Portico (29.1%) for lower rates of mean aortic valve gradients. CONCLUSIONS: The findings of the present study suggested that the device success rates were comparable among these new-generation valves except for DFM. After excluding DFM, Sapien 3 might be the best effective for decreased mortality and stroke; Lotus might be the best effective for decreased paravalvular leak; Evolut might be the best effective for decreased major and life-threatening bleeding and mean aortic valve gradients; Acurate and Portico might be the best effective for decreased permanent pacemaker implantation and acute kidney injury, respectively.


Asunto(s)
Lesión Renal Aguda , Estenosis de la Válvula Aórtica , Prótesis Valvulares Cardíacas , Accidente Cerebrovascular , Reemplazo de la Válvula Aórtica Transcatéter , Humanos , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Válvula Aórtica/cirugía , Metaanálisis en Red , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Resultado del Tratamiento , Diseño de Prótesis , Índice de Severidad de la Enfermedad , Estenosis de la Válvula Aórtica/cirugía
4.
bioRxiv ; 2023 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-37205582

RESUMEN

The common γ-chain (γc) family of cytokine receptors, including interleukin (IL)-2, IL-4, IL-7, IL-9, IL-15, and IL-21 receptors, are activated upon engagement with the common γc receptor in ligand dependent manner. Sharing of γc by the IL receptors (ILRs) is thought to be achieved by concomitant binding of γc and ILR ectodomains to a cytokine. Here, we found that direct interactions between the transmembrane domain (TMD) of γc and those of the ILRs are also required for receptor activation, and remarkably, the same γc TMD can specifically recognize multiple ILR TMDs of diverse sequences. Heterodimer structures of γc TMD bound to the TMDs of IL-7R and IL-9R, determined in near lipid bilayer environment, reveal a conserved knob-into-hole mechanism of recognition that mediates receptor sharing within the membrane. Functional mutagenesis data indicate the requirement of the heterotypic interactions of TMDs in signaling, which could explain disease mutations within the receptor TMDs. One-Sentence Summary: The transmembrane anchors of interleukin receptors of the gamma-chain family are critical for receptor sharing and activation.

5.
J Cardiovasc Dev Dis ; 10(1)2023 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-36661924

RESUMEN

BACKGROUND: The incidence of acute myocardial infarction (AMI) in the younger population has been increasing gradually in recent years. The objective of the present study is to investigate the safety and effectiveness of drug-eluting balloons (DEBs) in young patients with AMI. METHODS: All consecutive patients with AMI aged ≤ 45 years were retrospectively enrolled. The primary endpoint was a device-oriented composite endpoint (DOCE) of cardiac death, target vessel myocardial infarction (MI), or target lesion revascularization (TLR). The secondary study endpoints included heart failure and major bleeding events. RESULTS: A total of 276 young patients presenting with AMI were finally included. The median follow-up period was 1155 days. Patients treated with DEBs had a trend toward a lower incidence of DOCEs (3.0% vs. 11.0%, p = 0.12) mainly driven by the need for TLR (3.0% vs. 9.1%, p = 0.19) than those treated with DESs. No significant differences between the two groups were detected in the occurrence of cardiac death (0.0% vs. 0.5%, p = 0.69), MI (0.0% vs. 1.4%, p = 0.40), heart failure (0.0% vs. 1.9%, p = 0.39), or major bleeding events (1.5% vs 4.8%, p = 0.30). Multivariate regression analysis showed that DEBs were associated with a trend toward a lower risk of DOCEs (HR 0.13, 95% CI [0.02, 1.05], p = 0.06). CONCLUSIONS: The findings of the present study suggested that DEBs might be a potential treatment option in young patients with AMI. A larger scale, randomized, multicenter study is required to investigate the safety and effectiveness of DEBs in this setting.

6.
J Clin Med ; 12(2)2023 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-36675362

RESUMEN

BACKGROUND: Ischemia reperfusion injury (IRI) remains a major problem in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). We have developed a novel reperfusion strategy for PCI and named it "volume-controlled reperfusion (VCR)". The aim of the current study was to assess the safety and feasibility of VCR in patients with STEMI. METHODS: Consecutive patients admitted to Beijing Chaoyang Hospital with STEMI were prospectively enrolled. The feasibility endpoint was procedural success. The safety endpoints included death from all causes, major vascular complications, and major adverse cardiac event (MACE), i.e., a composite of cardiac death, myocardial reinfarction, target vessel revascularization (TVR), and heart failure. RESULTS: A total of 30 patients were finally included. Procedural success was achieved in 28 (93.3%) patients. No patients died during the study and no major vascular complications or MACE occurred during hospitalization. With the exception of one patient (3.3%) who underwent TVR three months after discharge, no patient encountered death (0.0%), major vascular complications (0.0%), or and other MACEs (0.0%) during the median follow-up of 16 months. CONCLUSION: The findings of the pilot study suggest that VCR has favorable feasibility and safety in patients with STEMI. Further larger randomized trials are required to evaluate the effectiveness of VCR in STEMI patients.

7.
Gut Microbes ; 14(1): 2145843, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36398889

RESUMEN

Imbalance of gut microbiota homeostasis is related to the occurrence of ulcerative colitis (UC), and probiotics are thought to modulate immune microenvironment and repair barrier function. Here, in order to reveal the interaction between UC and gut microbiota, we screened a new probiotic strain by 16S rRNA sequencing from Dextran Sulfate Sodium (DSS)-induced colitis mice, and explored the mechanism and clinical relevance. Lactobacillus johnsonii (L. johnsonii), as a potential anti-inflammatory bacterium was decreased colonization in colitis mice. Gavage L. johnsonii could alleviate colitis by specifically increasing the proportion of intestinal macrophages and the secretion of Il-10 with macrophages depleted model and in Il10-/- mice. We identified this subset of immune cells activated by L. johnsonii as CD206+ macrophagesIL-10. Mechanistically, L. johnsonii supplementation enhanced the mobilization of CD206+ macrophagesIL-10 through the activation of STAT3 in vivo and in vitro. In addition, we revealed that TLR1/2 was essential for the activation of STAT3 and the recognition of L. johnsonii by macrophages. Clinically, there was positive correlation between the abundance of L. johnsonii and the expression level of MRC1, IL10 and TLR1/2 in UC tissues. L. johnsonii could activate native macrophages into CD206+ macrophages and release IL-10 through TLR1/2-STAT3 pathway to relieve experimental colitis. L. johnsonii may serve as an immunomodulator and anti-inflammatory therapeutic target for UC.


Asunto(s)
Colitis Ulcerosa , Colitis , Microbioma Gastrointestinal , Lactobacillus johnsonii , Receptor Toll-Like 1 , Animales , Ratones , Antiinflamatorios , Colitis/genética , Colitis/microbiología , Colitis/terapia , Colitis Ulcerosa/genética , Colitis Ulcerosa/microbiología , Colitis Ulcerosa/terapia , Sulfato de Dextran/toxicidad , Interleucina-10/genética , Macrófagos , ARN Ribosómico 16S , Receptor Toll-Like 1/genética , Receptor Toll-Like 1/metabolismo
8.
Nature ; 612(7938): 156-161, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36228656

RESUMEN

The B cell antigen receptor (BCR) is composed of a membrane-bound class M, D, G, E or A immunoglobulin for antigen recognition1-3 and a disulfide-linked Igα (also known as CD79A) and Igß (also known as CD79B) heterodimer (Igα/ß) that functions as the signalling entity through intracellular immunoreceptor tyrosine-based activation motifs (ITAMs)4,5. The organizing principle of the BCR remains unknown. Here we report cryo-electron microscopy structures of mouse full-length IgM BCR and its Fab-deleted form. At the ectodomain (ECD), the Igα/ß heterodimer mainly uses Igα to associate with Cµ3 and Cµ4 domains of one heavy chain (µHC) while leaving the other heavy chain (µHC') unbound. The transmembrane domain (TMD) helices of µHC and µHC' interact with those of the Igα/ß heterodimer to form a tight four-helix bundle. The asymmetry at the TMD prevents the recruitment of two Igα/ß heterodimers. Notably, the connecting peptide between the ECD and TMD of µHC intervenes in between those of Igα and Igß to guide TMD assembly through charge complementarity. Weaker but distinct density for the Igß ITAM nestles next to the TMD, suggesting potential autoinhibition of ITAM phosphorylation. Interfacial analyses suggest that all BCR classes utilize a general organizational architecture. Our studies provide a structural platform for understanding B cell signalling and designing rational therapies against BCR-mediated diseases.


Asunto(s)
Microscopía por Crioelectrón , Receptores de Antígenos de Linfocitos B , Animales , Ratones , Linfocitos B/metabolismo , Receptores de Antígenos de Linfocitos B/biosíntesis , Receptores de Antígenos de Linfocitos B/química , Receptores de Antígenos de Linfocitos B/metabolismo , Receptores de Antígenos de Linfocitos B/ultraestructura , Transducción de Señal , Fragmentos Fab de Inmunoglobulinas , Dominios Proteicos , Fosforilación
9.
Science ; 376(6598): eabm9326, 2022 06 10.
Artículo en Inglés | MEDLINE | ID: mdl-35679401

RESUMEN

INTRODUCTION The nuclear pore complex (NPC) is the molecular conduit in the nuclear membrane of eukaryotic cells that regulates import and export of biomolecules between the nucleus and the cytosol, with vertebrate NPCs ~110 to 125 MDa in molecular mass and ~120 nm in diameter. NPCs are organized into four main rings: the cytoplasmic ring (CR) at the cytosolic side, the inner ring and the luminal ring on the plane of the nuclear membrane, and the nuclear ring facing the nucleus. Each ring possesses an approximate eightfold symmetry and is composed of multiple copies of different nucleoporins. NPCs have been implicated in numerous biological processes, and their dysfunctions are associated with a growing number of serious human diseases. However, despite pioneering studies from many groups over the past two decades, we still lack a full understanding of NPCs' organization, dynamics, and complexity. RATIONALE We used the Xenopus laevis oocyte as a model system for the structural characterization because each oocyte possesses a large number of NPC particles that can be visualized on native nuclear membranes without the aid of detergent extraction. We used single-particle cryo-electron microscopy (cryo-EM) analysis on data collected at different stage tilt angles for three-dimensional reconstruction and structure prediction with AlphaFold for model building. RESULTS We reconstructed the CR map of X. laevis NPC at 6.9 and 6.7 Å resolutions for the full CR protomer and a core region, respectively, and predicted the structures of the individual nucleoporins using AlphaFold because no high-resolution models of X. laevis Nups were available. For any ambiguous subunit interactions, we also predicted complex structures, which further guided model fitting of the CR protomer. We placed the nucleoporin or complex structures into the CR density to obtain an almost full CR atomic model, composed of the inner and outer Y-complexes, two copies of Nup205, two copies of the Nup214-Nup88-Nup62 complex, one Nup155, and five copies of Nup358. In particular, we predicted the largest protein in the NPC, Nup358, as having an S-shaped globular domain, a coiled-coil domain, and a largely disordered C-terminal region containing phenylalanine-glycine (FG) repeats previously shown to form a gel-like condensate phase for selective cargo passage. Four of the Nup358 copies clamp around the inner and outer Y-complexes to stabilize the CR, and the fifth Nup358 situates in the center of the cluster of clamps. AlphaFold also predicted a homo-oligomeric, likely specifically pentameric, coiled-coil structure of Nup358 that may provide the avidity for Nup358 recruitment to the NPC and for lowering the threshold for Nup358 condensation in NPC biogenesis. CONCLUSION Our studies offer an example of integrative cryo-EM and structure prediction as a general approach for attaining more precise models of megadalton protein complexes from medium-resolution density maps. The more accurate and almost complete model of the CR presented here expands our understanding of the molecular interactions in the NPC and represents a substantial step forward toward the molecular architecture of a full NPC, with implications for NPC function, biogenesis, and regulation. [Figure: see text].


Asunto(s)
Inteligencia Artificial , Proteínas de Complejo Poro Nuclear , Poro Nuclear , Proteínas de Xenopus , Animales , Microscopía por Crioelectrón , Citosol/metabolismo , Poro Nuclear/química , Proteínas de Complejo Poro Nuclear/química , Oocitos , Conformación Proteica , Subunidades de Proteína/metabolismo , Programas Informáticos , Proteínas de Xenopus/química , Xenopus laevis/metabolismo
10.
Cell Res ; 32(5): 437-450, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35301440

RESUMEN

Nuclear pore complexes (NPCs) mediate bidirectional nucleocytoplasmic transport of substances in eukaryotic cells. However, the accurate molecular arrangement of NPCs remains enigmatic owing to their huge size and highly dynamic nature. Here we determined the structure of the asymmetric unit of the inner ring (IR monomer) at 3.73 Å resolution by single-particle cryo-electron microscopy, and created an atomic model of the intact IR consisting of 192 molecules of 8 nucleoporins. In each IR monomer, the Z-shaped Nup188-Nup192 complex in the middle layer is sandwiched by two approximately parallel rhomboidal structures in the inner and outer layers, while Nup188, Nup192 and Nic96 link all subunits to constitute a relatively stable IR monomer. In contrast, the intact IR is assembled by loose and instable interactions between IR monomers. These structures, together with previously reported structural information of IR, reveal two distinct interaction modes between IR monomers and extensive flexible connections in IR assembly, providing a structural basis for the stability and malleability of IR.


Asunto(s)
Poro Nuclear , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Microscopía por Crioelectrón , Modelos Moleculares , Poro Nuclear/química , Proteínas de Complejo Poro Nuclear/química , Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/química
11.
J Thorac Dis ; 13(3): 1737-1745, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33841964

RESUMEN

BACKGROUND: This study aims to analyze the in-hospital outcome of primary percutaneous coronary intervention (PCI) for patients with acute myocardial infarction (AMI) and prior coronary artery bypass grafting (CABG). METHODS: This was a retrospective study. From January 2011 to December 2018, the data of 78 consecutive patients (study group) with prior CABG, who received primary coronary angiography in the setting of ST-elevation myocardial infarction (STEMI) or non-ST-elevation myocardial infarction (NSTEMI), were screened. The study group was compared with another well-matched 78 patients without a history of CABG (control group). The information of the coronary angiograms and clinical data of both groups were analyzed. Multivariate conditional logistic regression models were constructed to test the association between PCI success rate and the prior CABG at age ≥65 and <65 years, respectively. RESULTS: The results revealed that the primary PCI success rate in the study group was significantly lower than in the control group (67.9% vs. 92.3%, P<0.001) and in-hospital mortality was significantly higher than in control group (11.5% vs. 2.5%, P=0.03). The multivariate logistic regression analysis indicated that the primary PCI success rate was significantly associated with the history of prior CABG both in young patients [age <65 years; odds ratio (OR) =5.26, 95% confidence interval (CI): 1.69-16.47] and elderly (age ≥65 years; OR =13.76, 95% CI: 2.72-69.75). CONCLUSIONS: The patients who receive primary PCI with AMI and prior CABG have poor in-hospital outcomes, with low PCI success rates and high mortality.

12.
Cell Discov ; 7(1): 10, 2021 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-33589616

RESUMEN

Plants harvest light energy utilized for photosynthesis by light-harvesting complex I and II (LHCI and LHCII) surrounding photosystem I and II (PSI and PSII), respectively. During the evolution of green plants, moss is at an evolutionarily intermediate position from aquatic photosynthetic organisms to land plants, being the first photosynthetic organisms that landed. Here, we report the structure of the PSI-LHCI supercomplex from the moss Physcomitrella patens (Pp) at 3.23 Å resolution solved by cryo-electron microscopy. Our structure revealed that four Lhca subunits are associated with the PSI core in an order of Lhca1-Lhca5-Lhca2-Lhca3. This number is much decreased from 8 to 10, the number of subunits in most green algal PSI-LHCI, but the same as those of land plants. Although Pp PSI-LHCI has a similar structure as PSI-LHCI of land plants, it has Lhca5, instead of Lhca4, in the second position of Lhca, and several differences were found in the arrangement of chlorophylls among green algal, moss, and land plant PSI-LHCI. One chlorophyll, PsaF-Chl 305, which is found in the moss PSI-LHCI, is located at the gap region between the two middle Lhca subunits and the PSI core, and therefore may make the excitation energy transfer from LHCI to the core more efficient than that of land plants. On the other hand, energy-transfer paths at the two side Lhca subunits are relatively conserved. These results provide a structural basis for unravelling the mechanisms of light-energy harvesting and transfer in the moss PSI-LHCI, as well as important clues on the changes of PSI-LHCI after landing.

13.
Proc Natl Acad Sci U S A ; 118(5)2021 02 02.
Artículo en Inglés | MEDLINE | ID: mdl-33495333

RESUMEN

Photosystem II (PSII) is a multisubunit pigment-protein complex and catalyzes light-driven water oxidation, leading to the conversion of light energy into chemical energy and the release of molecular oxygen. Psb27 is a small thylakoid lumen-localized protein known to serve as an assembly factor for the biogenesis and repair of the PSII complex. The exact location and binding fashion of Psb27 in the intermediate PSII remain elusive. Here, we report the structure of a dimeric Psb27-PSII complex purified from a psbV deletion mutant (ΔPsbV) of the cyanobacterium Thermosynechococcus vulcanus, solved by cryo-electron microscopy. Our structure showed that Psb27 is associated with CP43 at the luminal side, with specific interactions formed between Helix 2 and Helix 3 of Psb27 and a loop region between Helix 3 and Helix 4 of CP43 (loop C) as well as the large, lumen-exposed and hydrophilic E-loop of CP43. The binding of Psb27 imposes some conflicts with the N-terminal region of PsbO and also induces some conformational changes in CP43, CP47, and D2. This makes PsbO unable to bind in the Psb27-PSII. Conformational changes also occurred in D1, PsbE, PsbF, and PsbZ; this, together with the conformational changes occurred in CP43, CP47, and D2, may prevent the binding of PsbU and induce dissociation of PsbJ. This structural information provides important insights into the regulation mechanism of Psb27 in the biogenesis and repair of PSII.


Asunto(s)
Proteínas Bacterianas/química , Complejo de Proteína del Fotosistema II/química , Multimerización de Proteína , Proteínas Bacterianas/aislamiento & purificación , Modelos Moleculares , Complejo de Proteína del Fotosistema II/aislamiento & purificación , Complejo de Proteína del Fotosistema II/metabolismo , Unión Proteica , Homología Estructural de Proteína , Thermosynechococcus/metabolismo
14.
Nat Commun ; 11(1): 5081, 2020 10 08.
Artículo en Inglés | MEDLINE | ID: mdl-33033236

RESUMEN

Diatom is an important group of marine algae and contributes to around 20% of the global photosynthetic carbon fixation. Photosystem I (PSI) of diatoms is associated with a large number of fucoxanthin-chlorophyll a/c proteins (FCPIs). We report the structure of PSI-FCPI from a diatom Chaetoceros gracilis at 2.38 Å resolution by single-particle cryo-electron microscopy. PSI-FCPI is a monomeric supercomplex consisting of 12 core and 24 antenna subunits (FCPIs), and 326 chlorophylls a, 34 chlorophylls c, 102 fucoxanthins, 35 diadinoxanthins, 18 ß-carotenes and some electron transfer cofactors. Two subunits designated PsaR and PsaS were found in the core, whereas several subunits were lost. The large number of pigments constitute a unique and huge network ensuring efficient energy harvesting, transfer and dissipation. These results provide a firm structural basis for unraveling the mechanisms of light-energy harvesting, transfer and quenching in the diatom PSI-FCPI, and also important clues to evolutionary changes of PSI-LHCI.


Asunto(s)
Proteínas de Unión a Clorofila/química , Diatomeas/metabolismo , Transferencia de Energía , Complejo de Proteína del Fotosistema I/química , Complejos de Proteína Captadores de Luz/química , Complejos de Proteína Captadores de Luz/metabolismo , Pigmentos Biológicos/química , Pigmentos Biológicos/metabolismo , Subunidades de Proteína/química
16.
FEBS J ; 287(11): 2191-2200, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-31854056

RESUMEN

In photosynthesis, light energy is captured by pigments bound to light-harvesting antenna proteins (LHC) that then transfer the energy to the photosystem (PS) cores to initiate photochemical reactions. The LHC proteins surround the PS cores to form PS-LHC supercomplexes. In order to adapt to a wide range of light environments, photosynthetic organisms have developed a large variety of pigments and antenna proteins to utilize the light energy efficiently under different environments. Diatoms are a group of important eukaryotic algae and possess fucoxanthin (Fx) chlorophyll a/c proteins (FCP) as antenna which have exceptional capabilities of harvesting blue-green light under water and dissipate excess energy under strong light conditions. We have solved the structure of a PSII-FCPII supercomplex from a centric diatom Chaetoceros gracilis by cryo-electron microscopy, and also the structure of an isolated FCP dimer from a pennate diatom Phaeodactylum tricornutum by X-ray crystallography at a high resolution. These results revealed the oligomerization states of FCPs distinctly different from those of LHCII found in the green lineage organisms, the detailed binding patterns of Chl c and Fxs, a huge pigment network, and extensive protein-protein, pigment-protein, and pigment-pigment interactions within the PSII-FCPII supercomplex. These results therefore provide a solid structural basis for examining the detailed mechanisms of the highly efficient energy transfer and quenching processes in diatoms.


Asunto(s)
Diatomeas/ultraestructura , Complejos de Proteína Captadores de Luz/genética , Fotosíntesis/genética , Complejo de Proteína del Fotosistema II/genética , Clorofila A/química , Clorofila A/genética , Microscopía por Crioelectrón , Diatomeas/química , Diatomeas/genética , Transferencia de Energía/genética , Complejos de Proteína Captadores de Luz/química , Complejos de Proteína Captadores de Luz/ultraestructura , Complejo de Proteína del Fotosistema II/ultraestructura , Xantófilas/química
17.
Science ; 365(6452)2019 08 02.
Artículo en Inglés | MEDLINE | ID: mdl-31371578

RESUMEN

Diatoms play important roles in global primary productivity and biogeochemical cycling of carbon, in part owing to the ability of their photosynthetic apparatus to adapt to rapidly changing light intensity. We report a cryo-electron microscopy structure of the photosystem II (PSII)-fucoxanthin (Fx) chlorophyll (Chl) a/c binding protein (FCPII) supercomplex from the centric diatom Chaetoceros gracilis The supercomplex comprises two protomers, each with two tetrameric and three monomeric FCPIIs around a PSII core that contains five extrinsic oxygen-evolving proteins at the lumenal surface. The structure reveals the arrangement of a huge pigment network that contributes to efficient light energy harvesting, transfer, and dissipation processes in the diatoms.


Asunto(s)
Proteínas de Unión a Clorofila/química , Diatomeas/enzimología , Complejo de Proteína del Fotosistema II/química , Carotenoides , Microscopía por Crioelectrón , Multimerización de Proteína
18.
Nat Plants ; 5(3): 263-272, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30850820

RESUMEN

Photosystem I (PSI) is a highly efficient natural light-energy converter, and has diverse light-harvesting antennas associated with its core in different photosynthetic organisms. In green algae, an extremely large light-harvesting complex I (LHCI) captures and transfers energy to the PSI core. Here, we report the structure of PSI-LHCI from a green alga Bryopsis corticulans at 3.49 Å resolution, obtained by single-particle cryo-electron microscopy, which revealed 13 core subunits including subunits characteristic of both prokaryotes and eukaryotes, and 10 light-harvesting complex a (Lhca) antennas that form a double semi-ring and an additional Lhca dimer, including a novel four-transmembrane-helix Lhca. In total, 244 chlorophylls were identified, some of which were located at key positions for the fast energy transfer. These results provide a firm structural basis for unravelling the mechanisms of light-energy harvesting, transfer and quenching in the green algal PSI-LHCI, and important clues as to how PSI-LHCI has changed during evolution.


Asunto(s)
Chlorophyta/química , Complejos de Proteína Captadores de Luz/química , Complejo de Proteína del Fotosistema I/química , Proteínas Algáceas/química , Proteínas Algáceas/metabolismo , Carotenoides/química , Carotenoides/metabolismo , Clorofila/química , Clorofila/metabolismo , Chlorophyta/genética , Microscopía por Crioelectrón , Transferencia de Energía , Evolución Molecular , Complejos de Proteína Captadores de Luz/genética , Complejos de Proteína Captadores de Luz/aislamiento & purificación , Complejos de Proteína Captadores de Luz/metabolismo , Modelos Moleculares , Complejo de Proteína del Fotosistema I/genética , Complejo de Proteína del Fotosistema I/aislamiento & purificación , Complejo de Proteína del Fotosistema I/metabolismo , Multimerización de Proteína , Subunidades de Proteína/química , Subunidades de Proteína/metabolismo
19.
Proc Natl Acad Sci U S A ; 115(17): 4423-4428, 2018 04 24.
Artículo en Inglés | MEDLINE | ID: mdl-29632169

RESUMEN

Photosystem I (PSI) is one of the two photosystems present in oxygenic photosynthetic organisms and functions to harvest and convert light energy into chemical energy in photosynthesis. In eukaryotic algae and higher plants, PSI consists of a core surrounded by variable species and numbers of light-harvesting complex (LHC)I proteins, forming a PSI-LHCI supercomplex. Here, we report cryo-EM structures of PSI-LHCR from the red alga Cyanidioschyzon merolae in two forms, one with three Lhcr subunits attached to the side, similar to that of higher plants, and the other with two additional Lhcr subunits attached to the opposite side, indicating an ancient form of PSI-LHCI. Furthermore, the red algal PSI core showed features of both cyanobacterial and higher plant PSI, suggesting an intermediate type during evolution from prokaryotes to eukaryotes. The structure of PsaO, existing in eukaryotic organisms, was identified in the PSI core and binds three chlorophylls a and may be important in harvesting energy and in mediating energy transfer from LHCII to the PSI core under state-2 conditions. Individual attaching sites of LHCRs with the core subunits were identified, and each Lhcr was found to contain 11 to 13 chlorophylls a and 5 zeaxanthins, which are apparently different from those of LHCs in plant PSI-LHCI. Together, our results reveal unique energy transfer pathways different from those of higher plant PSI-LHCI, its adaptation to the changing environment, and the possible changes of PSI-LHCI during evolution from prokaryotes to eukaryotes.


Asunto(s)
Complejos de Proteína Captadores de Luz/ultraestructura , Complejo de Proteína del Fotosistema I/ultraestructura , Rhodophyta/enzimología , Microscopía por Crioelectrón/métodos , Estructura Cuaternaria de Proteína , Rhodophyta/ultraestructura
20.
Int Heart J ; 58(6): 894-899, 2017 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-29118301

RESUMEN

Totally thoracosopic mitral valve replacement (MVR) has been applied to mitral stenosis for many years. Three working ports are usually necessary, among which the longest port ranges from 6 to 8 cm. This study aimed to determine the safety and feasibility of the two-incision totally thoracoscopic approach for MVR, with the longest incision of 3 cm.From January 2014 to February 2016, 90 patients with mitral valve stenosis were retrospectively analyzed. Thirty-six (40%) patients were included in the two-incision group and 54 patients were operated on using the sternotomy approach. Perioperative variables and postoperative 3-month follow-up data were analyzed.All patients underwent MVR. Tricuspid valvuloplasty was performed in 23 (25.5%) patients with the Kay technique. The mean total surgery time, cardiopulmonary bypass, and cross-clamp times were longer in the two-incision group (266 ± 42 versus 200 ± 38 minutes; 156 ± 23 versus 121 ± 21 minutes; 100 ± 17 versus 80 ± 17 minutes, respectively) (P < 0.05). The mean postoperative mechanical ventilation time was shorter in the two-incision group (8.6 ± 2.5 versus 11.2 ± 2.6 hours, respectively) (P < 0.05). The mean volume of blood drainage was less in the two-incision group (497 ± 120 versus 730 ± 198 mL, respectively) (P < 0.05). Reopening occurred in one (sternotomy group, 1.8%) patient. No deaths, perivalvular leakage, infectious endocarditis, atelectasis of the lungs, or moderate tricuspid regurgitation were found at the 3-month follow-up.The two-incision totally thoracoscopic approach for MVR is safe and feasible. Concomitant tricuspid valvuloplasty can be conveniently performed. However, further clinical data are needed in future studies.


Asunto(s)
Implantación de Prótesis de Válvulas Cardíacas/métodos , Prótesis Valvulares Cardíacas , Válvula Mitral , Toracoscopía/métodos , Adulto , Femenino , Implantación de Prótesis de Válvulas Cardíacas/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Toracoscopía/estadística & datos numéricos
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