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1.
Chem Commun (Camb) ; 56(21): 3147-3150, 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32057047

RESUMO

Amyloid fibrils, implicated in health and diseases, commonly exhibit a periodic twist trait relevant to the structures and dynamics of the fibrils. However, the origins and modulations of fibril twist in complex in vivo environments are not yet fully understood. Here we highlight an important factor that causes twist variations in amyloid fibril structures-the presence of surrounding surfaces. Using cholesterol-containing lipid bilayers with varying cholesterol contents, we have demonstrated via atomic force microscopy that amyloid-ß peptide fibrils initiated on membranes increase their average pitch size of twisting periodicity as the cholesterol content increases. These surface-induced twist variations arise from the enhanced hydrophobic interactions between the fibril and the surface distorting the torsional elastic energy of the fibril twisting as supported by a theory of an elastic model. These findings not only provide an important insight into fibril polymorphism phenomena resulting from the surface effects but also suggest a novel solution to modulate filament twisting on the nanoscale for biomaterials applications involving nanoscale features.


Assuntos
Amiloide/química , Colesterol/química , Bicamadas Lipídicas/química , Microscopia de Força Atômica , Tamanho da Partícula , Conformação Proteica , Propriedades de Superfície
3.
Chem Commun (Camb) ; 56(15): 2348-2351, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-31993621

RESUMO

A miniaturized mimic of the active site of a protease, chymotrypsin, was linked to a target recognition unit to generate "Miniature Artificial Proteases" (mAPs). Time-resolved MALDI-TOF data analyses indicated that mAPs cleaved every amide bond between Lys16-Phe20 of the amyloid ß fragment (Aß12-21) and Aß1-40, resulting in inhibition of fibrillization and disruption of the preformed amyloid. Such a platform may offer not only new therapeutic options against various amyloidoses but also novel routes for the selective knockdown of specific proteins.


Assuntos
Amiloide/metabolismo , Quimotripsina/metabolismo , Amiloide/química , Domínio Catalítico , Quimotripsina/química , Humanos , Modelos Moleculares , Estrutura Molecular
4.
Photochem Photobiol Sci ; 19(1): 29-33, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31932832

RESUMO

We demonstrate amyloid fibril (AF) decomposition induced by NIR-active upconversion nanoparticles complexed with photosensitisers. The process is triggered by upconversion, which initiates a photochemical reaction cascade that culminates in the generation of the highly reactive singlet-oxygen product 1O2 close to the amyloid superstructures, resulting in AF decomposition.


Assuntos
Amiloide/antagonistas & inibidores , Nanopartículas/química , Fármacos Fotossensibilizantes/farmacologia , Amiloide/metabolismo , Humanos , Raios Infravermelhos
6.
Brain Nerve ; 72(1): 23-34, 2020 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-31907330

RESUMO

There is an urgent need for Alzheimer's disease (AD) treatments because of the growing number of individuals with preclinical, prodromal, and dementia forms of AD. Unfortunately, there are few effective treatments for AD, and many drug development trials for AD ultimately have failed. Current AD clinical trials include disease-modifying therapies, symptomatic cognitive enhancers, and symptomatic agents addressing neuropsychiatric and behavioral changes. Disease modifying therapies include anti-amyloid agents and anti-tau agents, both of which contain small molecules, monoclonal antibodies, or biological therapies. Amyloid is the most common specific target in phase 3 and phase 2 disease modification trials. Recent drug development trials for AD include preclinical and prodromal populations. Although biomarkers are increasingly used in drug development for AD, they are not used uniformly for confirmation of AD diagnosis. Enrollment of earlier populations, new biomarkers (e.g., neurofilament light), novel outcomes (e.g., AD Composite Score [ADCOMS]), and innovative trial designs (e.g., futility analysis, Bayesian adaptive designs) are needed to develop effective drugs against AD.


Assuntos
Doença de Alzheimer , Amiloide , Proteínas Amiloidogênicas , Teorema de Bayes , Biomarcadores , Humanos
7.
Nat Commun ; 11(1): 571, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31996674

RESUMO

Aggregation of the Tau protein into fibrils defines progression of neurodegenerative diseases, including Alzheimer's Disease. The molecular basis for potentially toxic reactions of Tau aggregates is poorly understood. Here we show that π-stacking by Arginine side-chains drives protein binding to Tau fibrils. We mapped an aggregation-dependent interaction pattern of Tau. Fibrils recruit specifically aberrant interactors characterised by intrinsically disordered regions of atypical sequence features. Arginine residues are key to initiate these aberrant interactions. Crucial for scavenging is the guanidinium group of its side chain, not its charge, indicating a key role of π-stacking chemistry for driving aberrant fibril interactions. Remarkably, despite the non-hydrophobic interaction mode, the molecular chaperone Hsp90 can modulate aberrant fibril binding. Together, our data present a molecular mode of action for derailment of protein-protein interaction by neurotoxic fibrils.


Assuntos
Doença de Alzheimer/metabolismo , Amiloide/metabolismo , Arginina/metabolismo , Ligação Proteica , Proteínas tau/metabolismo , Doença de Alzheimer/genética , Sequência de Aminoácidos , Animais , Arginina/química , Progressão da Doença , Guanidina/metabolismo , Proteínas de Choque Térmico HSP90 , Humanos , Espectrometria de Massas , Chaperonas Moleculares , Agregados Proteicos , Domínios Proteicos , Dobramento de Proteína , Proteoma , Ratos , Análise de Sequência de Proteína , Proteínas tau/química , Proteínas tau/genética
8.
Chemistry ; 26(9): 1893, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-31961031

RESUMO

Invited for the cover of this issue is the group of András Perczel at Eötvös Loránd University, Budapest, Hungary and colleagues from Osaka University, Japan. The image depicts the amyloid buildup of an Exenatide derivate miniprotein (E5) monitored on a simplified hyperspace. Read the full text of the article at 10.1002/chem.201903826.


Assuntos
Amiloide/metabolismo , Amiloide/química , Modelos Biológicos , Ressonância Magnética Nuclear Biomolecular , Peptídeos/química , Peptídeos/metabolismo , Estrutura Secundária de Proteína , Termodinâmica
9.
Chem Biol Interact ; 315: 108884, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31678113

RESUMO

Quinolinic acid (QA) known as a neuro-active metabolite associated with the kynurenine pathway. At high concentrations, QA is often involved in the initiation and development of several human neurologic diseases, like Alzheimer's disease. Because of the QA action as the NMDA receptor, it is considered as a potent excitotoxin in vivo. Since it is probable that different mechanisms are employed by QA, activation of NMDA receptors cannot fully explain the revealed toxicity and it is even believed that there are multiple unknown mechanisms/targets leading to QA cytotoxicity. Herein we report accelerated amyloid oligomerization of 1N4R Tau under the effect of QA, in vitro, then the molecular structure, morphology and toxicity of the protein aggregate were documented by using various theoretical/experimental approaches. The possible mechanism of action of QA-induced Tau oligomerization has also been explored.


Assuntos
Amiloide/metabolismo , Neurotoxinas/efeitos adversos , Agregados Proteicos/efeitos dos fármacos , Piridinas/efeitos adversos , Ácido Quinolínico/efeitos adversos , Doença de Alzheimer/metabolismo , Humanos , Cinurenina/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo
10.
Chemistry ; 26(9): 1968-1978, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-31647140

RESUMO

The amyloid formation of the folded segment of a variant of Exenatide (a marketed drug for type-2 diabetes mellitus) was studied by electronic circular dichroism (ECD) and NMR spectroscopy. We found that the optimum temperature for E5 protein amyloidosis coincides with body temperature and requires well below physiological salt concentration. Decomposition of the ECD spectra and its barycentric representation on the folded-unfolded-amyloid potential energy surface allowed us to monitor the full range of molecular transformation of amyloidogenesis. We identified points of no return (e.g.; T=37 °C, pH 4.1, cE5 =250 µm, cNaCl =50 mm, t>4-6 h) that will inevitably gravitate into the amyloid state. The strong B-type far ultraviolet (FUV)-ECD spectra and an unexpectedly strong near ultraviolet (NUV)-ECD signal (Θ≈275-285   nm ) indicate that the amyloid phase of E5 is built from monomers of quasi-elongated backbone structure (φ≈-145°, ψ≈+145°) with strong interstrand Tyr↔Trp interaction. Misfolded intermediates and the buildup of "toxic" early-stage oligomers leading to self-association were identified and monitored as a function of time. Results indicate that the amyloid transition is triggered by subtle misfolding of the α-helix, exposing aromatic and hydrophobic side chains that may provide the first centers for an intermolecular reorganization. These initial clusters provide the spatial closeness and sufficient time for a transition to the ß-structured amyloid nucleus, thus the process follows a nucleated growth mechanism.


Assuntos
Amiloide/metabolismo , Sequência de Aminoácidos , Amiloide/química , Dicroísmo Circular , Concentração de Íons de Hidrogênio , Simulação de Dinâmica Molecular , Ressonância Magnética Nuclear Biomolecular , Peptídeos/química , Conformação Proteica , Dobramento de Proteína , Temperatura Ambiente
11.
J Photochem Photobiol B ; 202: 111671, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31731076

RESUMO

As a molecular chaperone, ß-casein is difficult to form amyloid fibrils under physiological conditions due to its chaperone activity. Heparan sulfate (HS) has drawn attention of technologists all over the word because of its relation to amyloid deposits in some amyloidosis diseases. For better understanding the relationship between the ß-casein and HS, the multi-spectroscopic studies were employed. The data of thioflavin T (ThT) binding assay, transmission electron microscopy (TEM) and circular dichroism (CD) demonstrated that HS promoted fibril formation by ß-casein in the amount and the growth speed. The results of steady-state UV-vis absorption spectra, fluorescence spectroscopy and fluorescence lifetime revealed that the ß-casein-HS complexes were formed and HS quenched the fluorescence of ß-casein by a static quenching mechanism. On the basis of fluorescence analysis, the value of binding constant was equal to 1.17 × 107 L mol-1 at 338.15 K and there was about one binding site between them. According to thermodynamic parameters obtained, it was deduced that a spontaneous reaction happened, and protein-ligand complex was stabilized by hydrogen bonds and hydrophobic interaction. Furthermore, using fluorescence resonance energy transfer (FRET) assay, the value of binding distance between HS and Trp143 of ß-casein was calculated to be 0.93 nm. Finally, on the basis of synchronous fluorescence experiment, the polarity increasing and hydrophobicity decreasing around Trp143 occurred during the period of fibril formation by ß-casein.


Assuntos
Amiloide/metabolismo , Caseínas/química , Heparitina Sulfato/química , Amiloide/química , Animais , Sítios de Ligação , Caseínas/metabolismo , Bovinos , Dicroísmo Circular , Transferência Ressonante de Energia de Fluorescência , Heparitina Sulfato/metabolismo , Interações Hidrofóbicas e Hidrofílicas , Microscopia Eletrônica de Transmissão , Ligação Proteica , Termodinâmica
12.
Clin Nucl Med ; 45(1): e8-e14, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31524679

RESUMO

PURPOSE: Based on the possibility that early-phase florbetaben (E-FBB) brain PET can be a surrogate for brain perfusion imaging, we conducted this study to investigate the clinical utility of E-FBB PET instead of F-FDG brain PET. MATERIALS AND METHODS: This prospective study included 35 patients with clinical suspicion of cognitive decline or dementia and 5 healthy controls. Brain MRI, E-FBB PET, late-phase FBB PET, and FDG PET were acquired. The regional SUV ratios (SUVRs) were calculated by cortical surface region of interest analysis using individual MRI, and relationship between E-FBB and FDG PET was analyzed. All PET scans were scored and analyzed as per visual scoring system, which represent tracer uptake abnormality. Moreover, uptake patterns were analyzed to determine the disease. RESULTS: Among the 40 subjects, 19 were amyloid-positive and 21 were amyloid-negative on late-phase FBB PET. Cortical surface region of interest analysis conducted for comparing between E-FBB and FDG PET revealed significant correlations (P < 0.0001) for regional SUVR among all brain regions; however, the SUVR values of FDG PET were statistically higher than those of E-FBB PET. Similarly, although the visually rated scores for E-FBB and FDG PET showed significant correlation (P < 0.0001), it was considered that the tracer uptake was more severely decreased for FDG PET. The disease types, specified by E-FBB and FDG PET, were statistically correlated. CONCLUSIONS: E-FBB PET could potentially be a useful biomarker for the diagnosis of dementia in place of FDG PET. Nevertheless, the severity of the disease was more accurately determined by FDG PET.


Assuntos
Compostos de Anilina , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons/métodos , Estilbenos , Idoso , Amiloide/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Estudos de Casos e Controles , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/metabolismo , Demência/diagnóstico por imagem , Demência/metabolismo , Feminino , Humanos , Masculino , Neuroimagem , Estudos Prospectivos , Fatores de Tempo
13.
Biophys Chem ; 256: 106281, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31756663

RESUMO

Timely and accurate diagnosis of Alzheimer's disease (AD) remains a major challenge in the medical arena. ß-amyloid (Aß) imaging techniques such as positron emission tomography and single photon emission computed tomography require the use of an imaging probe. To date, only flutemetamol, florbetaben and florbetapir have been approved for clinical use as imaging probes. Design of imaging probes requires a detailed understanding of disease mechanism(s) and receptor-ligand interaction. In this study, molecular docking, molecular dynamics and binding free energies were used to investigate the multiple binding sites exhibited by ß-amyloid fibrils. Protein atomic models 2BEG, 5KK3, 2M4J, 2LMN, 5OQV, 2NAO, 2MVX and 2MXU (protein databank codes) were used to investigate the nature and location of binding sites and binding profiles of selected molecules with known affinities. Although amyloid fibrils are known to have multiple binding sites, we demonstrated that model 2MXU possesses one site which is druggable and can bind with common scaffolds currently being used in the imaging of amyloid fibrils. Models 2NAO, 5KK3 and 2M4J revealed that even though multiple sites may be available in some fibrils, the entire protein may not have a druggable site. Molecular dynamics revealed atomic models 2MXU and 2MVX to be the least flexible among the list. The outcomes of this investigation can be translated to assist in designing novel molecules that can be used for brain imaging in Alzheimer's disease.


Assuntos
Amiloide/química , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Amiloide/metabolismo , Sítios de Ligação , Bases de Dados de Proteínas , Humanos , Ligantes , Ligação Proteica , Estrutura Terciária de Proteína
14.
Phys Chem Chem Phys ; 22(3): 1543-1556, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31872820

RESUMO

Amyloid aggregation modulators offer a promising treatment strategy for Alzheimer's disease (AD). We have recently reported a novel di-triazole based compound 6n as a multi-target-directed ligand (MTDL) against AD. 6n effectively inhibits Aß42 aggregation, metal-induced Aß42 aggregation, reactive oxygen species (ROS) generation, and rescues SH-SY5Y cells from Aß42 induced neurotoxicity. However, the underlying inhibitory mechanism remains uncovered. In this regard, molecular dynamics (MD) simulations were performed to understand the effect of 6n on the structure and stability of monomeric Aß42 and a pentameric protofibril structure of Aß42. Compound 6n binds preferably to the central hydrophobic core (CHC) and C-terminal regions of the Aß42 monomer as well as the protofibril structure. The secondary structure analysis suggests that 6n prevents the aggregation of the Aß42 monomer and disaggregates Aß42 protofibrils by sustaining the helical content in the Aß42 monomer and converting the ß-sheet into random coil conformation in the Aß42 protofibril structure. A significant decrease in the average number of hydrogen bonds, binding affinity, and residue-residue contacts between chains D-E of the Aß42 protofibril in the presence of 6n indicates destabilization of the Aß42 protofibril structure. The MM-PBSA (molecular mechanics Poisson-Boltzmann surface area) analysis highlighted favourable binding free energy (ΔGbinding) for the Aß42 monomer-6n and Aß42 protofibril-6n complex. Overall, MD results highlighted that 6n stabilizes the native α-helix conformation of the Aß42 monomer and induces a sizable destabilization in the Aß42 protofibril structure. This work provides theoretical insights into the inhibitory mechanism of 6n against amyloid aggregation and will be beneficial as a molecular guide for structure-based drug design against AD.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Fragmentos de Peptídeos/metabolismo , Triazóis/química , Amiloide/química , Amiloide/metabolismo , Peptídeos beta-Amiloides/química , Simulação de Dinâmica Molecular , Fragmentos de Peptídeos/química , Ligação Proteica , Conformação Proteica em alfa-Hélice , Estabilidade Proteica
15.
J Sci Food Agric ; 100(2): 607-613, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31591730

RESUMO

BACKGROUND: α-Dicarbonyl compounds are widely generated in the Maillard reaction, caramelization and oil oxidation during heat treatment. These compounds can readily react with lysine and arginine residues of a protein, whereas the influence of these compounds on protein structure and quality has seldom been revealed. This study compared influence of glycation by glucose and α-dicarbonyl compounds on amyloid-like aggregation of ß-lactoglobulin (ß-LG), both fibrillation kinetics and conformation of aggregates were studied. RESULTS: Compared with glycation by glucose, the glycation by α-dicarbonyl compounds resulted in faster reduction of free amino group, sulfydryl group, and the relative content of ß-sheet secondary structure, according to the ultraviolet (UV) spectra or circular dichroism (CD) spectra results. Based on the analysis of fibrillation kinetics using thioflavin T (ThT) binding assay, the glycation by α-dicarbonyls were more efficient in suppressing the growth of fibrillar aggregates. In addition, glycation by α-dicarbonyl resulted in amorphous oligomers, which were compared with the amyloid-like aggregates in control and glucose-glycated samples, based on the transmission electron microscopy (TEM) observation. CONCLUSIONS: Glycation by α-dicarbonyl compounds induced larger decline in the ß-sheet structure of ß-LG than glycation by glucose, and thus largely suppressed the amyloid-like aggregation of ß-LG and changed the morphology of aggregates. © 2019 Society of Chemical Industry.


Assuntos
Amiloide/química , Lactoglobulinas/química , Animais , Bovinos , Dicroísmo Circular , Glucose/química , Glicosilação , Temperatura Alta , Agregados Proteicos , Estrutura Secundária de Proteína
16.
Biochim Biophys Acta Proteins Proteom ; 1868(1): 140283, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31526870

RESUMO

The abnormal aggregation of human islet amyloid polypeptide (hIAPP) is a crucial pathogenic factor associated with type 2 diabetes (T2D). The development of effective inhibitors to prevent hIAPP aggregation is a common therapeutic strategy against T2D. Lithospermic acid (LA) is a natural compound with diversified biological activities. In this study, electrospray ionization coupled with ion mobility-mass spectrometry, thioflavin T fluorescence assay, Congo red binding assay, Nile red fluorescence assay, circular dichroism spectroscopy, transmission electron microscopy, cell toxicity, lactate dehydrogenase assay (LDH) assay and molecular docking were combined to explore the influence of LA on hIAPP aggregation. Results showed that LA had favorable binding affinity to hIAPP and formed hIAPP-LA complexes, which could alter the relative abundance of the compact and extended conformers and promoted the transition of extended structures to compact conformers. LA also displayed strong inhibitory actions on fibrillation and potential protective effects against hIAPP-induced cell toxicity. Therefore, the obtained results were useful to understand the possible inhibitory mechanism of LA on hIAPP aggregation and provided valuable reference for the screening of potent amyloid inhibitors.


Assuntos
Amiloide/metabolismo , Benzofuranos/farmacologia , Depsídeos/farmacologia , Polipeptídeo Amiloide das Ilhotas Pancreáticas/metabolismo , Animais , Morte Celular/efeitos dos fármacos , Linhagem Celular , Humanos , Polipeptídeo Amiloide das Ilhotas Pancreáticas/química , Simulação de Acoplamento Molecular , Conformação Proteica , Ratos
18.
Phys Chem Chem Phys ; 22(1): 203-211, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31799519

RESUMO

The formation of amyloid fibrils by α-synuclein (αS) protein inside the Lewy bodies and Lewy neurites is the prominent pathological hallmark of Parkinson's disease (PD). The fibrillation of αS in vitro is described by a nucleation-elongation process involving the formation of a critical nucleus. Finding the critical/smallest nuclei and effective inhibitors of αS aggregation is a crucial step for the development of drugs against PD. Recent experiments reported that dopamine (DA) and norepinephrine (NE), two prominent naturally occurring neurotransmitters, can effectively disrupt the preformed αS fibrils. The level of DA/NE in blood can be markedly increased by exercise. However, the size and structure of the critical nucleus and the disruptive mechanism by DA/NE are largely unknown. In this work, we performed multiple molecular dynamics (MD) simulations to find the critical nucleus size and examine the influences of DA/NE molecules on preformed αS44-96 (Greek-key-like core of full length αS) protofibrils. Our results show that the trimer is the critical nucleus for the αS44-96 fibril formation, and the tetramer is the minimal stable nucleus. When DA/NE molecules bind to the fibril-like trimer and tetramer, they strongly destabilize the αS protofibrils by disrupting the ß-sheet structure and inter-chain E46-K80 salt bridges. Two common binding sites are identified for both DA and NE molecules on αS oligomers: residues 57-70 and 81-83. A different binding site is also observed, which is located at the N-terminal region (residues 45-52). The binding of DA/NE molecules to αS oligomers is mostly driven by hydrophobic and electrostatic interactions. We found two disruptive modes, and binding to the turn region of αS oligomers but disrupting the adjacent ß-sheet structure is the dominant one. Our work identified the critical nucleus of Greek-key-like core of αS protofibrils and revealed the disruptive mechanism of αS protofibrils by DA/NE molecules, which may be helpful to the design of effective drugs against αS aggregation.


Assuntos
Dopamina/química , Norepinefrina/química , alfa-Sinucleína/química , Amiloide/metabolismo , Sítios de Ligação , Humanos , Simulação de Dinâmica Molecular , Norepinefrina/metabolismo , Ligação Proteica , Conformação Proteica , Eletricidade Estática
19.
J Phys Chem Lett ; 10(24): 7872-7877, 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31790267

RESUMO

The deposition of coassemblies made of the small presynaptic protein, α-synuclein, and lipids in the brains of patients is the hallmark of Parkinson's disease. In this study, we used natural abundance 13C and 31P magic-angle spinning nuclear magnetic resonance spectroscopy together with cryo-electron microscopy and differential scanning calorimetry to characterize the fibrils formed by α-synuclein in the presence of vesicles made of 1,2-dimyristoyl-sn-glycero-3-phospho-L-serine or 1,2-dilauroyl-sn-glycero-3-phospho-L-serine. Our results show that these lipids coassemble with α-synuclein molecules to give thin and curly amyloid fibrils. The coassembly leads to slower and more isotropic reorientation of lipid molecular segments and a decrease in both the temperature and enthalpy of the lipid chain-melting compared with those in the protein-free lipid lamellar phase. These findings provide new insights into the properties of lipids within protein-lipid assemblies that can be associated with Parkinson's disease.


Assuntos
Amiloide/química , Bicamadas Lipídicas/química , alfa-Sinucleína/química , Cinética , Estrutura Molecular , Transição de Fase , Ligação Proteica , Serina/química , Relação Estrutura-Atividade , Termodinâmica , Temperatura de Transição
20.
Mol Biol (Mosk) ; 53(6): 968-981, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31876276

RESUMO

This review summarizes the main achievements of recent years in molecular organization research of yeast cell surface, i.e., the compartment that consists of the coordinately functioning plasma membrane, periplasmic space, and cell wall. There are data on vesicular transport to the external environment through the cell wall and the formation of channels in the wall, which indicate the possibility of dynamic rearrangements of the molecular structure of the yeast cell wall. There is an idea about the mosaic arrangement of the compartments of the plasma membrane. The hypothesis has been suggested on the heterogeneity of the molecular structure of the cell wall, which is usually considered as uniform except for the budding zones. The groups of proteins that form the molecular assembly of the yeast cell surface have been described. Special attention has been paid for proteins with amyloid properties, including Bgl2p glucanosyltransglycosylase, which is important for virulence in pathogenic yeast, and Gas1p, the first of the studied proteins of the cell surface, which is involved in the regulation of ribosomal DNA transcriptional silencing. The data on the structure of receptors localized on the cell surface and the "moonlight" proteins, involved in the cell stress response of yeasts, have been given.


Assuntos
Membrana Celular/metabolismo , Parede Celular/metabolismo , Periplasma/metabolismo , Saccharomyces cerevisiae/citologia , Saccharomyces cerevisiae/metabolismo , Amiloide/química , Amiloide/metabolismo , Membrana Celular/química , Parede Celular/química , Periplasma/química , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/metabolismo
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