7x29
From Proteopedia
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<StructureSection load='7x29' size='340' side='right'caption='[[7x29]], [[Resolution|resolution]] 2.49Å' scene=''> | <StructureSection load='7x29' size='340' side='right'caption='[[7x29]], [[Resolution|resolution]] 2.49Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[7x29]] is a 7 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/ | + | <table><tr><td colspan='2'>[[7x29]] is a 7 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus_2 Severe acute respiratory syndrome coronavirus 2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7X29 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7X29 FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7x29 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7x29 OCA], [https://pdbe.org/7x29 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7x29 RCSB], [https://www.ebi.ac.uk/pdbsum/7x29 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7x29 ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.49Å</td></tr> |
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7x29 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7x29 OCA], [https://pdbe.org/7x29 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7x29 RCSB], [https://www.ebi.ac.uk/pdbsum/7x29 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7x29 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| - | == Function == | ||
| - | [https://www.uniprot.org/uniprot/K0BRG7_MERS K0BRG7_MERS] Spike protein S1: attaches the virion to the cell membrane by interacting with host receptor, initiating the infection.[HAMAP-Rule:MF_04099] Spike protein S2': Acts as a viral fusion peptide which is unmasked following S2 cleavage occurring upon virus endocytosis.[HAMAP-Rule:MF_04099] Spike protein S2: mediates fusion of the virion and cellular membranes by acting as a class I viral fusion protein. Under the current model, the protein has at least three conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes.[HAMAP-Rule:MF_04099] | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
Neutralizing monoclonal antibodies (mAbs) against highly pathogenic coronaviruses represent promising candidates for clinical intervention. Here, we isolated a potent neutralizing monoclonal antibody, MERS-S41, from a yeast displayed scFv library using the S protein as a bait. To uncover the neutralization mechanism, we determined structures of MERS-S41 Fab in complex with the trimeric spike glycoprotein by cryoelectron microscopy (cryo-EM). We observed four distinct classes of the complex structure, which showed that the MERS-S41 Fab bound to the "up" receptor binding domain (RBD) with full saturation and also bound to an accessible partially lifted "down" RBD, providing a structural basis for understanding how mAbs bind to trimeric spike glycoproteins. Structure analysis of the epitope and cell surface staining assays demonstrated that virus entry is blocked predominantly by direct competition with the host receptor, dipeptidyl peptidase-4 (DPP4). | Neutralizing monoclonal antibodies (mAbs) against highly pathogenic coronaviruses represent promising candidates for clinical intervention. Here, we isolated a potent neutralizing monoclonal antibody, MERS-S41, from a yeast displayed scFv library using the S protein as a bait. To uncover the neutralization mechanism, we determined structures of MERS-S41 Fab in complex with the trimeric spike glycoprotein by cryoelectron microscopy (cryo-EM). We observed four distinct classes of the complex structure, which showed that the MERS-S41 Fab bound to the "up" receptor binding domain (RBD) with full saturation and also bound to an accessible partially lifted "down" RBD, providing a structural basis for understanding how mAbs bind to trimeric spike glycoproteins. Structure analysis of the epitope and cell surface staining assays demonstrated that virus entry is blocked predominantly by direct competition with the host receptor, dipeptidyl peptidase-4 (DPP4). | ||
| - | Cryoelectron microscopy structures of a human neutralizing antibody bound to MERS-CoV spike glycoprotein.,Zhang S, Jia W, Zeng J, Li M, Wang Z, Zhou H, Zhang L, Wang X Front Microbiol. 2022 Sep 28;13:988298. doi: 10.3389/fmicb.2022.988298., eCollection 2022. PMID:36246239<ref>PMID:36246239</ref> | + | Cryoelectron microscopy structures of a human neutralizing antibody bound to MERS-CoV spike glycoprotein.,Zhang S, Jia W, Zeng J, Li M, Wang Z, Zhou H, Zhang L, Wang X Front Microbiol. 2022 Sep 28;13:988298. doi: 10.3389/fmicb.2022.988298. , eCollection 2022. PMID:36246239<ref>PMID:36246239</ref> |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Severe acute respiratory syndrome coronavirus 2]] |
[[Category: Wang XW]] | [[Category: Wang XW]] | ||
[[Category: Zeng JW]] | [[Category: Zeng JW]] | ||
[[Category: Zhang SY]] | [[Category: Zhang SY]] | ||
[[Category: Zhou HX]] | [[Category: Zhou HX]] | ||
Current revision
MERS-CoV spike complex with S41 neutralizing antibody Fab Class2 (1u2d RBD with 2Fab)
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