7u0e
From Proteopedia
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7u0e]] is a 6 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=7U0E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7U0E FirstGlance]. <br> | <table><tr><td colspan='2'>[[7u0e]] is a 6 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=7U0E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7U0E 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=7u0e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7u0e OCA], [https://pdbe.org/7u0e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7u0e RCSB], [https://www.ebi.ac.uk/pdbsum/7u0e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7u0e ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</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=7u0e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7u0e OCA], [https://pdbe.org/7u0e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7u0e RCSB], [https://www.ebi.ac.uk/pdbsum/7u0e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7u0e ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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The coronavirus spike glycoprotein attaches to host receptors and mediates viral fusion. Using a broad screening approach, we isolated seven monoclonal antibodies (mAbs) that bind to all human-infecting coronavirus spike proteins from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune donors. These mAbs recognize the fusion peptide and acquire affinity and breadth through somatic mutations. Despite targeting a conserved motif, only some mAbs show broad neutralizing activity in vitro against alpha- and betacoronaviruses, including animal coronaviruses WIV-1 and PDF-2180. Two selected mAbs also neutralize Omicron BA.1 and BA.2 authentic viruses and reduce viral burden and pathology in vivo. Structural and functional analyses showed that the fusion peptide-specific mAbs bound with different modalities to a cryptic epitope hidden in prefusion stabilized spike, which became exposed upon binding of angiotensin-converting enzyme 2 (ACE2) or ACE2-mimicking mAbs. | The coronavirus spike glycoprotein attaches to host receptors and mediates viral fusion. Using a broad screening approach, we isolated seven monoclonal antibodies (mAbs) that bind to all human-infecting coronavirus spike proteins from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune donors. These mAbs recognize the fusion peptide and acquire affinity and breadth through somatic mutations. Despite targeting a conserved motif, only some mAbs show broad neutralizing activity in vitro against alpha- and betacoronaviruses, including animal coronaviruses WIV-1 and PDF-2180. Two selected mAbs also neutralize Omicron BA.1 and BA.2 authentic viruses and reduce viral burden and pathology in vivo. Structural and functional analyses showed that the fusion peptide-specific mAbs bound with different modalities to a cryptic epitope hidden in prefusion stabilized spike, which became exposed upon binding of angiotensin-converting enzyme 2 (ACE2) or ACE2-mimicking mAbs. | ||
| - | ACE2-binding exposes the SARS-CoV-2 fusion peptide to broadly neutralizing coronavirus antibodies.,Low JS, Jerak J, Tortorici MA, McCallum M, Pinto D, Cassotta A, Foglierini M, Mele F, Abdelnabi R, Weynand B, Noack J, Montiel-Ruiz M, Bianchi S, Benigni F, Sprugasci N, Joshi A, Bowen JE, Stewart C, Rexhepaj M, Walls AC, Jarrossay D, Morone D, Paparoditis P, Garzoni C, Ferrari P, Ceschi A, Neyts J, Purcell LA, Snell G, Corti D, Lanzavecchia A, Veesler D, Sallusto F Science. 2022 Aug 12;377(6607):735-742. doi: 10.1126/science.abq2679. Epub 2022, Jul 12. PMID:35857703<ref>PMID:35857703</ref> | + | ACE2-binding exposes the SARS-CoV-2 fusion peptide to broadly neutralizing coronavirus antibodies.,Low JS, Jerak J, Tortorici MA, McCallum M, Pinto D, Cassotta A, Foglierini M, Mele F, Abdelnabi R, Weynand B, Noack J, Montiel-Ruiz M, Bianchi S, Benigni F, Sprugasci N, Joshi A, Bowen JE, Stewart C, Rexhepaj M, Walls AC, Jarrossay D, Morone D, Paparoditis P, Garzoni C, Ferrari P, Ceschi A, Neyts J, Purcell LA, Snell G, Corti D, Lanzavecchia A, Veesler D, Sallusto F Science. 2022 Aug 12;377(6607):735-742. doi: 10.1126/science.abq2679. Epub 2022 , Jul 12. PMID:35857703<ref>PMID:35857703</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> | ||
Current revision
Crystal Structure of C13C9 Fab in complex with SARS-CoV-2 S fusion peptide
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