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Image-processing pipelines require the design of complex workflows combining many different steps that bring the raw acquired data to a final result with biological meaning. In the image-processing domain of cryo-electron microscopy single-particle analysis (cryo-EM SPA), hundreds of steps must be performed to obtain the three-dimensional structure of a biological macromolecule by integrating data spread over thousands of micrographs containing millions of copies of allegedly the same macromolecule. The execution of such complicated workflows demands a specific tool to keep track of all these steps performed. Additionally, due to the extremely low signal-to-noise ratio (SNR), the estimation of any image parameter is heavily affected by noise resulting in a significant fraction of incorrect estimates. Although low SNR and processing millions of images by hundreds of sequential steps requiring substantial computational resources are specific to cryo-EM, these characteristics may be shared by other biological imaging domains. Here, we present Scipion, a Python generic open-source workflow engine specifically adapted for image processing. Its main characteristics are: (a) interoperability, (b) smart object model, (c) gluing operations, (d) comparison operations, (e) wide set of domain-specific operations, (f) execution in streaming, (g) smooth integration in high-performance computing environments, (h) execution with and without graphical capabilities, (i) flexible visualization, (j) user authentication and private access to private data, (k) scripting capabilities, (l) high performance, (m) traceability, (n) reproducibility, (o) self-reporting, (p) reusability, (q) extensibility, (r) software updates, and (s) non-restrictive software licensing.
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Single-particle cryo-electron microscopy has become a powerful technique for the 3D structure determination of biological molecules. The last decade has seen an astonishing development of both hardware and software, and an exponential growth of new structures obtained at medium-high resolution. However, the knowledge accumulated in this field over the years has hardly been utilized as feedback in the reconstruction of new structures. In this context, this article explores the use of the deep-learning approach deepEMhancer as a regularizer in the RELION refinement process. deepEMhancer introduces prior information derived from macromolecular structures, and contributes to noise reduction and signal enhancement, as well as a higher degree of isotropy. These features have a direct effect on image alignment and reduction of overfitting during iterative refinement. The advantages of this combination are demonstrated for several membrane proteins, for which it is especially useful because of their high disorder and flexibility.
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Photosystem I (PSI) is one of two photosystems involved in oxygenic photosynthesis. PSI of cyanobacteria exists in monomeric, trimeric, and tetrameric forms, in contrast to the strictly monomeric form of PSI in plants and algae. The tetrameric organization raises questions about its structural, physiological, and evolutionary significance. Here we report the â¼3.72 Å resolution cryo-electron microscopy structure of tetrameric PSI from the thermophilic, unicellular cyanobacterium Chroococcidiopsis sp. TS-821. The structure resolves 44 subunits and 448 cofactor molecules. We conclude that the tetramer is arranged via two different interfaces resulting from a dimer-of-dimers organization. The localization of chlorophyll molecules permits an excitation energy pathway within and between adjacent monomers. Bioinformatics analysis reveals conserved regions in the PsaL subunit that correlate with the oligomeric state. Tetrameric PSI may function as a key evolutionary step between the trimeric and monomeric forms of PSI organization in photosynthetic organisms.
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Cianobacterias , Complejo de Proteína del Fotosistema I , Clorofila , Microscopía por Crioelectrón , Cianobacterias/química , Cianobacterias/metabolismo , Fotosíntesis , Complejo de Proteína del Fotosistema I/química , Complejo de Proteína del Fotosistema I/metabolismoRESUMEN
Xmipp is an open-source software package consisting of multiple programs for processing data originating from electron microscopy and electron tomography, designed and managed by the Biocomputing Unit of the Spanish National Center for Biotechnology, although with contributions from many other developers over the world. During its 25 years of existence, Xmipp underwent multiple changes and updates. While there were many publications related to new programs and functionality added to Xmipp, there is no single publication on the Xmipp as a package since 2013. In this article, we give an overview of the changes and new work since 2013, describe technologies and techniques used during the development, and take a peek at the future of the package.
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SUMMARY: The web platform 3DBionotes-WS integrates multiple web services and an interactive web viewer to provide a unified environment in which biological annotations can be analyzed in their structural context. Since the COVID-19 outbreak, new structural data from many viral proteins have been provided at a very fast pace. This effort includes many cryogenic electron microscopy (cryo-EM) studies, together with more traditional ones (X-rays, NMR), using several modeling approaches and complemented with structural predictions. At the same time, a plethora of new genomics and interactomics information (including fragment screening and structure-based virtual screening efforts) have been made available from different servers. In this context, we have developed 3DBionotes-COVID-19 as an answer to: (i) the need to explore multiomics data in a unified context with a special focus on structural information and (ii) the drive to incorporate quality measurements, especially in the form of advanced validation metrics for cryo-EM. AVAILABILITY AND IMPLEMENTATION: https://3dbionotes.cnb.csic.es/ws/covid19. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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COVID-19 , Programas Informáticos , Humanos , GenómicaRESUMEN
Cryo-electron microscopy has established as a mature structural biology technique to elucidate the three-dimensional structure of biological macromolecules. The Coulomb potential of the sample is imaged by an electron beam, and fast semi-conductor detectors produce movies of the sample under study. These movies have to be further processed by a whole pipeline of image-processing algorithms that produce the final structure of the macromolecule. In this chapter, we illustrate this whole processing pipeline putting in value the strength of "meta algorithms," which are the combination of several algorithms, each one with different mathematical rationale, in order to distinguish correctly from incorrectly estimated parameters. We show how this strategy leads to superior performance of the whole pipeline as well as more confident assessments about the reconstructed structures. The "meta algorithms" strategy is common to many fields and, in particular, it has provided excellent results in bioinformatics. We illustrate this combination using the workflow engine, Scipion.
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Algoritmos , Microscopía por Crioelectrón/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Imagenología Tridimensional/métodos , Imagen Individual de Molécula/métodos , Biología Computacional , Sustancias Macromoleculares/ultraestructura , Biología Molecular/métodos , Flujo de TrabajoRESUMEN
In recent years, advances in cryoEM have dramatically increased the resolution of reconstructions and, with it, the number of solved atomic models. It is widely accepted that the quality of cryoEM maps varies locally; therefore, the evaluation of the maps-derived structural models must be done locally as well. In this article, a method for the local analysis of the map-to-model fit is presented. The algorithm uses a comparison of two local resolution maps. The first is the local FSC (Fourier shell correlation) between the full map and the model, while the second is calculated between the half maps normally used in typical single particle analysis workflows. We call the quality measure "FSC-Q", and it is a quantitative estimation of how much of the model is supported by the signal content of the map. Furthermore, we show that FSC-Q may be helpful to detect overfitting. It can be used to complement other methods, such as the Q-score method that estimates the resolvability of atoms.
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Algoritmos , Microscopía por Crioelectrón , Análisis de Fourier , Modelos Moleculares , Receptores Acoplados a Proteínas G/química , Glicoproteína de la Espiga del Coronavirus/químicaRESUMEN
Using a new consensus-based image-processing approach together with principal component analysis, the flexibility and conformational dynamics of the SARS-CoV-2 spike in the prefusion state have been analysed. These studies revealed concerted motions involving the receptor-binding domain (RBD), N-terminal domain, and subdomains 1 and 2 around the previously characterized 1-RBD-up state, which have been modeled as elastic deformations. It is shown that in this data set there are not well defined, stable spike conformations, but virtually a continuum of states. An ensemble map was obtained with minimum bias, from which the extremes of the change along the direction of maximal variance were modeled by flexible fitting. The results provide a warning of the potential image-processing classification instability of these complicated data sets, which has a direct impact on the interpretability of the results.
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With the help of novel processing workflows and algorithms, we have obtained a better understanding of the flexibility and conformational dynamics of the SARS-CoV-2 spike in the prefusion state. We have re-analyzed previous cryo-EM data combining 3D clustering approaches with ways to explore a continuous flexibility space based on 3D Principal Component Analysis. These advanced analyses revealed a concerted motion involving the receptor-binding domain (RBD), N-terminal domain (NTD), and subdomain 1 and 2 (SD1 & SD2) around the previously characterized 1-RBD-up state, which have been modeled as elastic deformations. We show that in this dataset there are not well-defined, stable, spike conformations, but virtually a continuum of states moving in a concerted fashion. We obtained an improved resolution ensemble map with minimum bias, from which we model by flexible fitting the extremes of the change along the direction of maximal variance. Moreover, a high-resolution structure of a recently described biochemically stabilized form of the spike is shown to greatly reduce the dynamics observed for the wild-type spike. Our results provide new detailed avenues to potentially restrain the spike dynamics for structure-based drug and vaccine design and at the same time give a warning of the potential image processing classification instability of these complicated datasets, having a direct impact on the interpretability of the results.
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MOTIVATION: Recent technological advances and computational developments have allowed the reconstruction of Cryo-Electron Microscopy (cryo-EM) maps at near-atomic resolution. On a typical workflow and once the cryo-EM map has been calculated, a sharpening process is usually performed to enhance map visualization, a step that has proven very important in the key task of structural modeling. However, sharpening approaches, in general, neglects the local quality of the map, which is clearly suboptimal. RESULTS: Here, a new method for local sharpening of cryo-EM density maps is proposed. The algorithm, named LocalDeblur, is based on a local resolution-guided Wiener restoration approach of the original map. The method is fully automatic and, from the user point of view, virtually parameter-free, without requiring either a starting model or introducing any additional structure factor correction or boosting. Results clearly show a significant impact on map interpretability, greatly helping modeling. In particular, this local sharpening approach is especially suitable for maps that present a broad resolution range, as is often the case for membrane proteins or macromolecules with high flexibility, all of them otherwise very suitable and interesting specimens for cryo-EM. To our knowledge, and leaving out the use of local filters, it represents the first application of local resolution in cryo-EM sharpening. AVAILABILITY AND IMPLEMENTATION: The source code (LocalDeblur) can be found at https://github.com/I2PC/xmipp and can be run using Scipion (http://scipion.cnb.csic.es) (release numbers greater than or equal 1.2.1). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Programas Informáticos , Microscopía por Crioelectrón , Sustancias Macromoleculares , Modelos Moleculares , Conformación ProteicaRESUMEN
In this article, a method is presented to estimate a new local quality measure for 3D cryoEM maps that adopts the form of a 'local resolution' type of information. The algorithm (DeepRes) is based on deep-learning 3D feature detection. DeepRes is fully automatic and parameter-free, and avoids the issues of most current methods, such as their insensitivity to enhancements owing to B-factor sharpening (unless the 3D mask is changed), among others, which is an issue that has been virtually neglected in the cryoEM field until now. In this way, DeepRes can be applied to any map, detecting subtle changes in local quality after applying enhancement processes such as isotropic filters or substantially more complex procedures, such as model-based local sharpening, non-model-based methods or denoising, that may be very difficult to follow using current methods. It performs as a human observer expects. The comparison with traditional local resolution indicators is also addressed.
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MOTIVATION: Cryo electron microscopy (EM) is currently one of the main tools to reveal the structural information of biological macromolecules. The re-construction of three-dimensional (3D) maps is typically carried out following an iterative process that requires an initial estimation of the 3D map to be refined in subsequent steps. Therefore, its determination is key in the quality of the final results, and there are cases in which it is still an open issue in single particle analysis (SPA). Small angle X-ray scattering (SAXS) is a well-known technique applied to structural biology. It is useful from small nanostructures up to macromolecular ensembles for its ability to obtain low resolution information of the biological sample measuring its X-ray scattering curve. These curves, together with further analysis, are able to yield information on the sizes, shapes and structures of the analyzed particles. RESULTS: In this paper, we show how the low resolution structural information revealed by SAXS is very useful for the validation of EM initial 3D models in SPA, helping the following refinement process to obtain more accurate 3D structures. For this purpose, we approximate the initial map by pseudo-atoms and predict the SAXS curve expected for this pseudo-atomic structure. The match between the predicted and experimental SAXS curves is considered as a good sign of the correctness of the EM initial map. AVAILABILITY AND IMPLEMENTATION: The algorithm is freely available as part of the Scipion 1.2 software at http://scipion.i2pc.es/.
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Microscopía por Crioelectrón , Dispersión del Ángulo Pequeño , Difracción de Rayos X , Rayos XRESUMEN
The calcitonin receptor (CTR) is a class B G protein-coupled receptor (GPCR) that responds to the peptide hormone calcitonin (CT). CTs are clinically approved for the treatment of bone diseases. We previously reported a 4.1 Å structure of the activated CTR bound to salmon CT (sCT) and heterotrimeric Gs protein by cryo-electron microscopy (Liang, Y.-L., et al. Phase-plate cryo- EM structure of a class B GPCR-G protein complex. Nature 2017, 546, 118-123). In the current study, we have reprocessed the electron micrographs to yield a 3.3 Å map of the complex. This has allowed us to model extracellular loops (ECLs) 2 and 3, and the peptide N-terminus that previously could not be resolved. We have also performed alanine scanning mutagenesis of ECL1 and the upper segment of transmembrane helix 1 (TM1) and its extension into the receptor extracellular domain (TM1 stalk), with effects on peptide binding and function assessed by cAMP accumulation and ERK1/2 phosphorylation. These data were combined with previously published alanine scanning mutagenesis of ECL2 and ECL3 and the new structural information to provide a comprehensive 3D map of the molecular surface of the CTR that controls binding and signaling of distinct CT and related peptides. The work highlights distinctions in how different, related, class B receptors may be activated. The new mutational data on the TM1 stalk and ECL1 have also provided critical insights into the divergent control of cAMP versus pERK signaling and, collectively with previous mutagenesis data, offer evidence that the conformations linked to these different signaling pathways are, in many ways, mutually exclusive. This study furthers our understanding of the complex nature of signaling elicited by GPCRs and, in particular, that of the therapeutically important class B subfamily.
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FtsZ is a self-assembling GTPase that forms, below the inner membrane, the mid-cell Z-ring guiding bacterial division. FtsZ monomers polymerize head to tail forming tubulin-like dynamic protofilaments, whose organization in the Z-ring is an unresolved problem. Rather than forming a well-defined structure, FtsZ protofilaments laterally associate in vitro into polymorphic condensates typically imaged on surfaces. We describe here nanoscale self-organizing properties of FtsZ assemblies in solution that underlie Z-ring assembly, employing time-resolved x-ray scattering and cryo-electron microscopy. We find that FtsZ forms bundles made of loosely bound filaments of variable length and curvature. Individual FtsZ protofilaments further bend upon nucleotide hydrolysis, highlighted by the observation of some large circular structures with 2.5-5° curvature angles between subunits, followed by disassembly end-products consisting of highly curved oligomers and 16-subunit -220 Å diameter mini-rings, here observed by cryo-electron microscopy. Neighbor FtsZ filaments in bundles are laterally spaced 70 Å, leaving a gap in between. In contrast, close contact between filament core structures (â¼50 Å spacing) is observed in straight polymers of FtsZ constructs lacking the C-terminal tail, which is known to provide a flexible tether essential for FtsZ functions in cell division. Changing the length of the intrinsically disordered C-tail linker modifies the interfilament spacing. We propose that the linker prevents dynamic FtsZ protofilaments in bundles from sticking to one another, holding them apart at a distance similar to the lateral spacing observed by electron cryotomography in several bacteria and liposomes. According to this model, weak interactions between curved polar FtsZ protofilaments through their the C-tails may facilitate the coherent treadmilling dynamics of membrane-associated FtsZ bundles in reconstituted systems, as well as the recently discovered movement of FtsZ clusters around bacterial Z-rings that is powered by GTP hydrolysis and guides correct septal cell wall synthesis and cell division.
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Proteínas Arqueales/metabolismo , Proteínas Bacterianas/metabolismo , Proteínas del Citoesqueleto/metabolismo , Proteínas Arqueales/química , Bacillus subtilis , Proteínas Bacterianas/química , Microscopía por Crioelectrón , Proteínas del Citoesqueleto/química , Escherichia coli , Hidrólisis , Methanocaldococcus , Modelos Moleculares , Polímeros , Dominios Proteicos , Multimerización de Proteína , Dispersión del Ángulo Pequeño , Soluciones/química , Difracción de Rayos XRESUMEN
FtsZ is a widely conserved tubulin-like GTPase that directs bacterial cell division and a new target for antibiotic discovery. This protein assembly machine cooperatively polymerizes forming single-stranded filaments, by means of self-switching between inactive and actively associating monomer conformations. The structural switch mechanism was proposed to involve a movement of the C-terminal and N-terminal FtsZ domains, opening a cleft between them, allosterically coupled to the formation of a tight association interface between consecutive subunits along the filament. The effective antibacterial benzamide PC190723 binds into the open interdomain cleft and stabilizes FtsZ filaments, thus impairing correct formation of the FtsZ ring for cell division. We have designed fluorescent analogs of PC190723 to probe the FtsZ structural assembly switch. Among them, nitrobenzoxadiazole probes specifically bind to assembled FtsZ rather than to monomers. Probes with several spacer lengths between the fluorophore and benzamide moieties suggest a binding site extension along the interdomain cleft. These probes label FtsZ rings of live Bacillus subtilis and Staphylococcus aureus, without apparently modifying normal cell morphology and growth, but at high concentrations they induce impaired bacterial division phenotypes typical of benzamide antibacterials. During the FtsZ assembly-disassembly process, the fluorescence anisotropy of the probes changes upon binding and dissociating from FtsZ, thus reporting open and closed FtsZ interdomain clefts. Our results demonstrate the structural mechanism of the FtsZ assembly switch, and suggest that the probes bind into the open clefts in cellular FtsZ polymers preferably to unassembled FtsZ in the bacterial cytosol.
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Proteins that associate with microtubules (MTs) are crucial to generate MT arrays and establish different cellular architectures. One example is PRC1 (protein regulator of cytokinesis 1), which cross-links antiparallel MTs and is essential for the completion of mitosis and cytokinesis. Here we describe a 4-Å-resolution cryo-EM structure of monomeric PRC1 bound to MTs. Residues in the spectrin domain of PRC1 contacting the MT are highly conserved and interact with the same pocket recognized by kinesin. We additionally found that PRC1 promotes MT assembly even in the presence of the MT stabilizer taxol. Interestingly, the angle of the spectrin domain on the MT surface corresponds to the previously observed cross-bridge angle between MTs cross-linked by full-length, dimeric PRC1. This finding, together with molecular dynamic simulations describing the intrinsic flexibility of PRC1, suggests that the MT-spectrin domain interface determines the geometry of the MT arrays cross-linked by PRC1.
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Proteínas de Ciclo Celular/ultraestructura , Cinesinas/ultraestructura , Microtúbulos/ultraestructura , Subunidades de Proteína/química , Tubulina (Proteína)/ultraestructura , Secuencias de Aminoácidos , Animales , Sitios de Unión , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Microscopía por Crioelectrón , Cristalografía por Rayos X , Expresión Génica , Humanos , Cinesinas/genética , Cinesinas/metabolismo , Microtúbulos/metabolismo , Simulación de Dinámica Molecular , Paclitaxel/química , Unión Proteica , Conformación Proteica en Hélice alfa , Conformación Proteica en Lámina beta , Dominios y Motivos de Interacción de Proteínas , Multimerización de Proteína , Subunidades de Proteína/genética , Subunidades de Proteína/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/ultraestructura , Porcinos , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/químicaRESUMEN
UNLABELLED: The prediction of protein-protein complexes from the structures of unbound components is a challenging and powerful strategy to decipher the mechanism of many essential biological processes. We present a user-friendly protein-protein docking server based on an improved version of FRODOCK that includes a complementary knowledge-based potential. The web interface provides a very effective tool to explore and select protein-protein models and interactively screen them against experimental distance constraints. The competitive success rates and efficiency achieved allow the retrieval of reliable potential protein-protein binding conformations that can be further refined with more computationally demanding strategies. AVAILABILITY AND IMPLEMENTATION: The server is free and open to all users with no login requirement at http://frodock.chaconlab.org CONTACT: pablo@chaconlab.org SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Computadores , Conformación Proteica , Proteínas , Programas InformáticosRESUMEN
Essential cell division protein FtsZ is considered an attractive target in the search for antibacterials with novel mechanisms of action to overcome the resistance problem. FtsZ undergoes GTP-dependent assembly at midcell to form the Z-ring, a dynamic structure that evolves until final constriction of the cell. Therefore, molecules able to inhibit its activity will eventually disrupt bacterial viability. In this work, we report a new series of small molecules able to replace GTP and to specifically inhibit FtsZ, blocking the bacterial division process. These new synthesized inhibitors interact with the GTP-binding site of FtsZ (Kd = 0.4-0.8 µM), display antibacterial activity against Gram-positive pathogenic bacteria, and show selectivity against tubulin. Biphenyl derivative 28 stands out as a potent FtsZ inhibitor (Kd = 0.5 µM) with high antibacterial activity [MIC (MRSA) = 7 µM]. In-depth analysis of the mechanism of action of compounds 22, 28, 33, and 36 has revealed that they act as effective inhibitors of correct FtsZ assembly, blocking bacterial division and thus leading to filamentous undivided cells. These findings provide a compelling rationale for the development of compounds targeting the GTP-binding site as antibacterial agents and open the door to antibiotics with novel mechanisms of action.
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Antibacterianos/síntesis química , Bacillus subtilis/efectos de los fármacos , Proteínas Bacterianas/antagonistas & inhibidores , Compuestos de Bifenilo/síntesis química , Proteínas del Citoesqueleto/antagonistas & inhibidores , Guanosina Trifosfato/química , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Naftalenos/síntesis química , Antibacterianos/química , Antibacterianos/farmacología , Bacillus subtilis/química , Bacillus subtilis/crecimiento & desarrollo , Proteínas Bacterianas/química , Sitios de Unión , Compuestos de Bifenilo/química , Compuestos de Bifenilo/farmacología , Proteínas del Citoesqueleto/química , Cinética , Staphylococcus aureus Resistente a Meticilina/química , Staphylococcus aureus Resistente a Meticilina/crecimiento & desarrollo , Pruebas de Sensibilidad Microbiana , Modelos Moleculares , Naftalenos/química , Naftalenos/farmacología , Unión Proteica , Estructura Secundaria de Proteína , Estructura Terciaria de Proteína , Relación Estructura-ActividadRESUMEN
SIGN-R1 is a principal receptor for microbial polysaccharides uptake and is responsible for C3 fixation via an unusual complement activation pathway on splenic marginal zone macrophages. In these macrophages, SIGN-R1 is also involved in anti-inflammatory activity of intravenous immunoglobulin by direct interaction with sialylated Fcs. The high-resolution crystal structures of SIGN-R1 carbohydrate recognition domain and its complexes with dextran sulfate or sialic acid, and of the sialylated Fc antibody provide insights into SIGN-R1's selective recognition of a-2,6-sialylated glycoproteins. Unexpectedly, an additional binding site has been found in the SIGNR1 carbohydrate recognition domain, structurally separate from the calcium-dependent carbohydrate-binding site. This secondary binding site could bind repetitive molecular patterns, as observed in microbial polysaccharides, in a calcium-independent manner. These two binding sites may allow SIGNR1 to simultaneously bind both immune glycoproteins and microbial polysaccharide components, accommodating SIGN-R1's ability to relate the recognition of microbes to the activation of the classical complement pathway.
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Moléculas de Adhesión Celular/química , Moléculas de Adhesión Celular/metabolismo , Sulfato de Dextran/metabolismo , Fragmentos Fc de Inmunoglobulinas/metabolismo , Lectinas Tipo C/química , Lectinas Tipo C/metabolismo , Ácido N-Acetilneuramínico/metabolismo , Receptores de Superficie Celular/química , Receptores de Superficie Celular/metabolismo , Animales , Sitios de Unión , Células CHO , Cricetulus , Cristalografía por Rayos X , Humanos , Ratones , Modelos Moleculares , Estructura Secundaria de ProteínaRESUMEN
Bacterial cytoskeletal protein FtsZ assembles in a head-to-tail manner, forming dynamic filaments that are essential for cell division. Here, we study their dynamics using unbiased atomistic molecular simulations from representative filament crystal structures. In agreement with experimental data, we find different filament curvatures that are supported by a nucleotide-regulated hinge motion between consecutive FtsZ monomers. Whereas GTP-FtsZ filaments bend and twist in a preferred orientation, thereby burying the nucleotide, the differently curved GDP-FtsZ filaments exhibit a heterogeneous distribution of open and closed interfaces between monomers. We identify a coordinated Mg(2+) ion as the key structural element in closing the nucleotide site and stabilizing GTP filaments, whereas the loss of the contacts with loop T7 from the next monomer in GDP filaments leads to open interfaces that are more prone to depolymerization. We monitored the FtsZ monomer assembly switch, which involves opening/closing of the cleft between the C-terminal domain and the H7 helix, and observed the relaxation of isolated and filament minus-end monomers into the closed-cleft inactive conformation. This result validates the proposed switch between the low-affinity monomeric closed-cleft conformation and the active open-cleft FtsZ conformation within filaments. Finally, we observed how the antibiotic PC190723 suppresses the disassembly switch and allosterically induces closure of the intermonomer interfaces, thus stabilizing the filament. Our studies provide detailed structural and dynamic insights into modulation of both the intrinsic curvature of the FtsZ filaments and the molecular switch coupled to the high-affinity end-wise association of FtsZ monomers.