2ghw

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{{STRUCTURE_2ghw| PDB=2ghw | SCENE= }}
 
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===Crystal structure of SARS spike protein receptor binding domain in complex with a neutralizing antibody, 80R===
 
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{{ABSTRACT_PUBMED_16954221}}
 
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==Function==
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==Crystal structure of SARS spike protein receptor binding domain in complex with a neutralizing antibody, 80R==
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[[http://www.uniprot.org/uniprot/SPIKE_CVHSA SPIKE_CVHSA]] S1 attaches the virion to the cell membrane by interacting with human ACE2 and CLEC4M/DC-SIGNR, initiating the infection. Binding to the receptor and internalization of the virus into the endosomes of the host cell probably induces conformational changes in the S glycoprotein. Proteolysis by cathepsin CTSL may unmask the fusion peptide of S2 and activate membranes fusion within endosomes. S2 is 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.
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<StructureSection load='2ghw' size='340' side='right'caption='[[2ghw]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2ghw]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome-related_coronavirus Severe acute respiratory syndrome-related coronavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GHW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GHW FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2ghw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ghw OCA], [https://pdbe.org/2ghw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ghw RCSB], [https://www.ebi.ac.uk/pdbsum/2ghw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ghw ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/SPIKE_SARS SPIKE_SARS] May down-regulate host tetherin (BST2) by lysosomal degradation, thereby counteracting its antiviral activity.<ref>PMID:31199522</ref> Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection (By similarity). Binding to human ACE2 and CLEC4M/DC-SIGNR receptors and internalization of the virus into the endosomes of the host cell induces conformational changes in the S glycoprotein. Proteolysis by cathepsin CTSL may unmask the fusion peptide of S2 and activate membrane fusion within endosomes.[HAMAP-Rule:MF_04099]<ref>PMID:14670965</ref> <ref>PMID:15496474</ref> 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] Acts as a viral fusion peptide which is unmasked following S2 cleavage occurring upon virus endocytosis.[HAMAP-Rule:MF_04099]<ref>PMID:19321428</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gh/2ghw_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2ghw ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Severe acute respiratory syndrome (SARS) is a newly emerged infectious disease that caused pandemic spread in 2003. The etiological agent of SARS is a novel coronavirus (SARS-CoV). The coronaviral surface spike protein S is a type I transmembrane glycoprotein that mediates initial host binding via the cell surface receptor angiotensin-converting enzyme 2 (ACE2), as well as the subsequent membrane fusion events required for cell entry. Here we report the crystal structure of the S1 receptor binding domain (RBD) in complex with a neutralizing antibody, 80R, at 2.3 A resolution, as well as the structure of the uncomplexed S1 RBD at 2.2 A resolution. We show that the 80R-binding epitope on the S1 RBD overlaps very closely with the ACE2-binding site, providing a rationale for the strong binding and broad neutralizing ability of the antibody. We provide a structural basis for the differential effects of certain mutations in the spike protein on 80R versus ACE2 binding, including escape mutants, which should facilitate the design of immunotherapeutics to treat a future SARS outbreak. We further show that the RBD of S1 forms dimers via an extensive interface that is disrupted in receptor- and antibody-bound crystal structures, and we propose a role for the dimer in virus stability and infectivity.
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==About this Structure==
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Structural basis of neutralization by a human anti-severe acute respiratory syndrome spike protein antibody, 80R.,Hwang WC, Lin Y, Santelli E, Sui J, Jaroszewski L, Stec B, Farzan M, Marasco WA, Liddington RC J Biol Chem. 2006 Nov 10;281(45):34610-6. Epub 2006 Sep 5. PMID:16954221<ref>PMID:16954221</ref>
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[[2ghw]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Sars_coronavirus Sars coronavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GHW OCA].
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==See Also==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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*[[Monoclonal Antibody|Monoclonal Antibody]]
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</div>
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<div class="pdbe-citations 2ghw" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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<ref group="xtra">PMID:016954221</ref><references group="xtra"/><references/>
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*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
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*[[Sandbox 3001|Sandbox 3001]]
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*[[Spike protein 3D structures|Spike protein 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Sars coronavirus]]
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[[Category: Large Structures]]
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[[Category: Farzan, M.]]
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[[Category: Severe acute respiratory syndrome-related coronavirus]]
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[[Category: Hwang, W C.]]
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[[Category: Farzan M]]
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[[Category: Jaroszewski, L.]]
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[[Category: Hwang WC]]
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[[Category: Liddington, R C.]]
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[[Category: Jaroszewski L]]
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[[Category: Lin, Y.]]
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[[Category: Liddington RC]]
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[[Category: Marasco, W A.]]
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[[Category: Lin Y]]
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[[Category: Santelli, E.]]
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[[Category: Marasco WA]]
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[[Category: Stec, B.]]
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[[Category: Santelli E]]
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[[Category: Sui, J.]]
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[[Category: Stec B]]
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[[Category: Neutralizing antibody]]
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[[Category: Sui J]]
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[[Category: S protein]]
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[[Category: Sar]]
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[[Category: Virus-viral protein-antibiotic complex]]
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Current revision

Crystal structure of SARS spike protein receptor binding domain in complex with a neutralizing antibody, 80R

PDB ID 2ghw

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