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==X-ray crystal structure of the SARS coronavirus spike receptor binding domain in complex with F26G19 Fab==
==X-ray crystal structure of the SARS coronavirus spike receptor binding domain in complex with F26G19 Fab==
<StructureSection load='3bgf' size='340' side='right' caption='[[3bgf]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
<StructureSection load='3bgf' size='340' side='right'caption='[[3bgf]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3bgf]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Cvhsa Cvhsa] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BGF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3BGF FirstGlance]. <br>
<table><tr><td colspan='2'>[[3bgf]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] 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=3BGF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BGF FirstGlance]. <br>
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2ajf|2ajf]], [[2dd8|2dd8]], [[2ghw|2ghw]], [[2ghv|2ghv]]</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]] 3&#8491;</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">S ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=227859 CVHSA])</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=3bgf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bgf OCA], [https://pdbe.org/3bgf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bgf RCSB], [https://www.ebi.ac.uk/pdbsum/3bgf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bgf ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3bgf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bgf OCA], [http://pdbe.org/3bgf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3bgf RCSB], [http://www.ebi.ac.uk/pdbsum/3bgf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3bgf ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[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.  
[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>
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
Check<jmol>
   <jmolCheckbox>
   <jmolCheckbox>
     <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bg/3bgf_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bg/3bgf_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
   </jmolCheckbox>
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==See Also==
==See Also==
*[[3D structures of monoclonal antibody|3D structures of monoclonal antibody]]
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
*[[Sandbox 3001|Sandbox 3001]]
*[[Spike protein 3D structures|Spike protein 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Cvhsa]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
[[Category: Pak, J E]]
[[Category: Severe acute respiratory syndrome-related coronavirus]]
[[Category: Rini, J M]]
[[Category: Pak JE]]
[[Category: Antigen-antibody complex]]
[[Category: Rini JM]]
[[Category: Envelope protein]]
[[Category: Glycoprotein]]
[[Category: Host-virus interaction]]
[[Category: Membrane]]
[[Category: Transmembrane]]
[[Category: Viral protein-immune system complex]]
[[Category: Virion]]
[[Category: Virulence]]

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