View source for 5i08


==Prefusion structure of a human coronavirus spike protein==
<SX load='5i08' size='340' side='right' viewer='molstar' caption='[[5i08]], [[Resolution|resolution]] 4.04&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5i08]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_virus_T4 Escherichia virus T4] and [https://en.wikipedia.org/wiki/Human_coronavirus_HKU1_(isolate_N5) Human coronavirus HKU1 (isolate N5)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I08 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5I08 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]] 4.04&#8491;</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=5i08 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i08 OCA], [https://pdbe.org/5i08 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5i08 RCSB], [https://www.ebi.ac.uk/pdbsum/5i08 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5i08 ProSAT]</span></td></tr>
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== Function ==
[https://www.uniprot.org/uniprot/SPIKE_CVHN5 SPIKE_CVHN5] S1 attaches the virion to the cell membrane by interacting with cell receptors, initiating the infection.  S2 is a 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 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. Presumably interacts with target cell lipid raft after cell attachment (By similarity).[https://www.uniprot.org/uniprot/M1E1E4_9HIV1 M1E1E4_9HIV1] 
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== Publication Abstract from PubMed ==
HKU1 is a human betacoronavirus that causes mild yet prevalent respiratory disease, and is related to the zoonotic SARS and MERS betacoronaviruses, which have high fatality rates and pandemic potential. Cell tropism and host range is determined in part by the coronavirus spike (S) protein, which binds cellular receptors and mediates membrane fusion. As the largest known class I fusion protein, its size and extensive glycosylation have hindered structural studies of the full ectodomain, thus preventing a molecular understanding of its function and limiting development of effective interventions. Here we present the 4.0 A resolution structure of the trimeric HKU1 S protein determined using single-particle cryo-electron microscopy. In the pre-fusion conformation, the receptor-binding subunits, S1, rest above the fusion-mediating subunits, S2, preventing their conformational rearrangement. Surprisingly, the S1 C-terminal domains are interdigitated and form extensive quaternary interactions that occlude surfaces known in other coronaviruses to bind protein receptors. These features, along with the location of the two protease sites known to be important for coronavirus entry, provide a structural basis to support a model of membrane fusion mediated by progressive S protein destabilization through receptor binding and proteolytic cleavage. These studies should also serve as a foundation for the structure-based design of betacoronavirus vaccine immunogens.

Pre-fusion structure of a human coronavirus spike protein.,Kirchdoerfer RN, Cottrell CA, Wang N, Pallesen J, Yassine HM, Turner HL, Corbett KS, Graham BS, McLellan JS, Ward AB Nature. 2016 Mar 3;531(7592):118-21. doi: 10.1038/nature17200. PMID:26935699<ref>PMID:26935699</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
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[[Category: Escherichia virus T4]]
[[Category: Large Structures]]
[[Category: Corbett KS]]
[[Category: Cottrell CA]]
[[Category: Graham BS]]
[[Category: Kirchdoerfer RN]]
[[Category: McLellan JS]]
[[Category: Pallesen J]]
[[Category: Turner HL]]
[[Category: Wang N]]
[[Category: Ward AB]]
[[Category: Yassine HM]]