6xkl
From Proteopedia
(Difference between revisions)
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==SARS-CoV-2 HexaPro S One RBD up== | ==SARS-CoV-2 HexaPro S One RBD up== | ||
- | <StructureSection load='6xkl' size='340' side='right'caption='[[6xkl]]' scene=''> | + | <StructureSection load='6xkl' size='340' side='right'caption='[[6xkl]], [[Resolution|resolution]] 3.21Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
- | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XKL OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6XKL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6xkl]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/2019-ncov 2019-ncov]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XKL OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6XKL FirstGlance]. <br> |
- | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6xkl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xkl OCA], [http://pdbe.org/6xkl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6xkl RCSB], [http://www.ebi.ac.uk/pdbsum/6xkl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6xkl ProSAT]</span></td></tr> | + | </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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">S, 2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=2697049 2019-nCoV])</td></tr> | ||
+ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6xkl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xkl OCA], [http://pdbe.org/6xkl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6xkl RCSB], [http://www.ebi.ac.uk/pdbsum/6xkl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6xkl ProSAT]</span></td></tr> | ||
</table> | </table> | ||
+ | == Function == | ||
+ | [[http://www.uniprot.org/uniprot/SPIKE_SARS2 SPIKE_SARS2]] attaches the virion to the cell membrane by interacting with host receptor, initiating the infection (By similarity). Binding to human ACE2 receptor and internalization of the virus into the endosomes of the host cell induces conformational changes in the Spike glycoprotein (PubMed:32142651, PubMed:32075877, PubMed:32155444). Uses also human TMPRSS2 for priming in human lung cells which is an essential step for viral entry (PubMed:32142651). Proteolysis by cathepsin CTSL may unmask the fusion peptide of S2 and activate membranes fusion within endosomes.[HAMAP-Rule:MF_04099]<ref>PMID:32075877</ref> <ref>PMID:32142651</ref> <ref>PMID:32155444</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] | ||
+ | <div style="background-color:#fffaf0;"> | ||
+ | == Publication Abstract from PubMed == | ||
+ | The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 has led to accelerated efforts to develop therapeutics, diagnostics, and vaccines to mitigate this public health emergency. A key target of these efforts is the spike (S) protein, a large trimeric class I fusion protein that is metastable and difficult to produce recombinantly in large quantities. Here, we designed and expressed over 100 structure-guided spike variants based upon a previously determined cryo-EM structure of the prefusion SARS-CoV-2 spike. Biochemical, biophysical and structural characterization of these variants identified numerous individual substitutions that increased protein yields and stability. The best variant, HexaPro, has six beneficial proline substitutions leading to ~10-fold higher expression than its parental construct and is able to withstand heat stress, storage at room temperature, and multiple freeze-thaws. A 3.2 A-resolution cryo-EM structure of HexaPro confirmed that it retains the prefusion spike conformation. High-yield production of a stabilized prefusion spike protein will accelerate the development of vaccines and serological diagnostics for SARS-CoV-2. | ||
+ | |||
+ | Structure-based Design of Prefusion-stabilized SARS-CoV-2 Spikes.,Hsieh CL, Goldsmith JA, Schaub JM, DiVenere AM, Kuo HC, Javanmardi K, Le KC, Wrapp D, Lee AG, Liu Y, Chou CW, Byrne PO, Hjorth CK, Johnson NV, Ludes-Meyers J, Nguyen AW, Park J, Wang N, Amengor D, Maynard JA, Finkelstein IJ, McLellan JS bioRxiv. 2020 May 30. doi: 10.1101/2020.05.30.125484. PMID:32577660<ref>PMID:32577660</ref> | ||
+ | |||
+ | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
+ | </div> | ||
+ | <div class="pdbe-citations 6xkl" style="background-color:#fffaf0;"></div> | ||
+ | == References == | ||
+ | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
+ | [[Category: 2019-ncov]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
- | [[Category: Goldsmith | + | [[Category: Goldsmith, J A]] |
- | [[Category: Hsieh C | + | [[Category: Hsieh, C L]] |
- | [[Category: McLellan | + | [[Category: McLellan, J S]] |
- | [[Category: Wrapp D]] | + | [[Category: Wrapp, D]] |
+ | [[Category: Fusion protein]] | ||
+ | [[Category: Glycoprotein]] | ||
+ | [[Category: Sars-cov-2]] | ||
+ | [[Category: Viral protein]] |
Revision as of 11:39, 29 July 2020
SARS-CoV-2 HexaPro S One RBD up
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