8dg9
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Cryo-EM Structure of RSV prefusion F trimer in complex with three MxR Fabs== | |
| + | <StructureSection load='8dg9' size='340' side='right'caption='[[8dg9]], [[Resolution|resolution]] 2.24Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8dg9]] is a 9 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Respiratory_syncytial_virus_A2 Respiratory syncytial virus A2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8DG9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DG9 FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.24Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=8dg9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dg9 OCA], [https://pdbe.org/8dg9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dg9 RCSB], [https://www.ebi.ac.uk/pdbsum/8dg9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dg9 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/FUS_HRSVA FUS_HRSVA] Class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and plasma cell membrane fusion, the heptad repeat (HR) regions 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 plasma cell membranes. Directs fusion of viral and cellular membranes leading to delivery of the nucleocapsid into the cytoplasm. This fusion is pH independent and occurs directly at the outer cell membrane. The trimer of F1-F2 (protein F) interacts with glycoprotein G at the virion surface. Upon binding of G to heparan sulfate, the hydrophobic fusion peptide is unmasked and interacts with the cellular membrane, inducing the fusion between host cell and virion membranes. Notably, RSV fusion protein is able to interact directly with heparan sulfate and therefore actively participates in virus attachment. Furthermore, the F2 subunit was identifed as the major determinant of RSV host cell specificity. Later in infection, proteins F expressed at the plasma membrane of infected cells mediate fusion with adjacent cells to form syncytia, a cytopathic effect that could lead to tissue necrosis. The fusion protein is also able to trigger p53-dependent apoptosis.<ref>PMID:12663767</ref> <ref>PMID:18216092</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Respiratory syncytial virus (RSV), human metapneumovirus (HMPV), and human parainfluenza virus types one (HPIV1) and three (HPIV3) can cause severe disease and death in immunocompromised patients, the elderly, and those with underlying lung disease. A protective monoclonal antibody exists for RSV, but clinical use is limited to high-risk infant populations. Hence, therapeutic options for these viruses in vulnerable patient populations are currently limited. Here, we present the discovery, in vitro characterization, and in vivo efficacy testing of two cross-neutralizing monoclonal antibodies, one targeting both HPIV3 and HPIV1 and the other targeting both RSV and HMPV. The 3 x 1 antibody is capable of targeting multiple parainfluenza viruses; the MxR antibody shares features with other previously reported monoclonal antibodies that are capable of neutralizing both RSV and HMPV. We obtained structures using cryo-electron microscopy of these antibodies in complex with their antigens at 3.62 A resolution for 3 x 1 bound to HPIV3 and at 2.24 A for MxR bound to RSV, providing a structural basis for in vitro binding and neutralization. Together, a cocktail of 3 x 1 and MxR could have clinical utility in providing broad protection against four of the respiratory viruses that cause significant morbidity and mortality in at-risk individuals. | ||
| - | + | Cross-protective antibodies against common endemic respiratory viruses.,Caban M, Rodarte JV, Bibby M, Gray MD, Taylor JJ, Pancera M, Boonyaratanakornkit J Nat Commun. 2023 Feb 13;14(1):798. doi: 10.1038/s41467-023-36459-3. PMID:36781872<ref>PMID:36781872</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 8dg9" style="background-color:#fffaf0;"></div> |
| - | [[Category: Pancera | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Respiratory syncytial virus A2]] | ||
| + | [[Category: Pancera M]] | ||
| + | [[Category: Rodarte JV]] | ||
Current revision
Cryo-EM Structure of RSV prefusion F trimer in complex with three MxR Fabs
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