6cs0
From Proteopedia
(Difference between revisions)
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<StructureSection load='6cs0' size='340' side='right' caption='[[6cs0]], [[Resolution|resolution]] 3.80Å' scene=''> | <StructureSection load='6cs0' size='340' side='right' caption='[[6cs0]], [[Resolution|resolution]] 3.80Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6cs0]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/ | + | <table><tr><td colspan='2'>[[6cs0]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Bpt4 Bpt4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CS0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CS0 FirstGlance]. <br> |
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | ||
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">wac, T4Tp161 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id= | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">wac, T4Tp161 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10665 BPT4])</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=6cs0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cs0 OCA], [http://pdbe.org/6cs0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cs0 RCSB], [http://www.ebi.ac.uk/pdbsum/6cs0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cs0 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=6cs0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cs0 OCA], [http://pdbe.org/6cs0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cs0 RCSB], [http://www.ebi.ac.uk/pdbsum/6cs0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cs0 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. | [[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. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2002 as a highly transmissible pathogenic human betacoronavirus. The viral spike glycoprotein (S) utilizes angiotensin-converting enzyme 2 (ACE2) as a host protein receptor and mediates fusion of the viral and host membranes, making S essential to viral entry into host cells and host species tropism. As SARS-CoV enters host cells, the viral S is believed to undergo a number of conformational transitions as it is cleaved by host proteases and binds to host receptors. We recently developed stabilizing mutations for coronavirus spikes that prevent the transition from the pre-fusion to post-fusion states. Here, we present cryo-EM analyses of a stabilized trimeric SARS-CoV S, as well as the trypsin-cleaved, stabilized S, and its interactions with ACE2. Neither binding to ACE2 nor cleavage by trypsin at the S1/S2 cleavage site impart large conformational changes within stabilized SARS-CoV S or expose the secondary cleavage site, S2'. | ||
| + | |||
| + | Stabilized coronavirus spikes are resistant to conformational changes induced by receptor recognition or proteolysis.,Kirchdoerfer RN, Wang N, Pallesen J, Wrapp D, Turner HL, Cottrell CA, Corbett KS, Graham BS, McLellan JS, Ward AB Sci Rep. 2018 Oct 24;8(1):15701. doi: 10.1038/s41598-018-34171-7. PMID:30356097<ref>PMID:30356097</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6cs0" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Fibritin|Fibritin]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Bpt4]] | ||
[[Category: Cottrell, C A]] | [[Category: Cottrell, C A]] | ||
[[Category: Kirchdoerfer, R N]] | [[Category: Kirchdoerfer, R N]] | ||
Revision as of 07:12, 12 December 2018
SARS Spike Glycoprotein, Trypsin-cleaved, Stabilized variant, one S1 CTD in an upwards conformation
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