6nb6

From Proteopedia

(Difference between revisions)

Revision as of 08:32, 6 March 2019

SARS-CoV complex with human neutralizing S230 antibody Fab fragment (state 1)

Structural highlights

6nb6 is a 7 chain structure with sequence from Cvhsa and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	6nb3, 6nb4, 6nb5, 6nb7, 6nb8
Gene:	S, 2 (CVHSA)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.

Publication Abstract from PubMed

Recent outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome, along with the threat of a future coronavirus-mediated pandemic, underscore the importance of finding ways to combat these viruses. The trimeric spike transmembrane glycoprotein S mediates entry into host cells and is the major target of neutralizing antibodies. To understand the humoral immune response elicited upon natural infections with coronaviruses, we structurally characterized the SARS-CoV and MERS-CoV S glycoproteins in complex with neutralizing antibodies isolated from human survivors. Although the two antibodies studied blocked attachment to the host cell receptor, only the anti-SARS-CoV S antibody triggered fusogenic conformational changes via receptor functional mimicry. These results provide a structural framework for understanding coronavirus neutralization by human antibodies and shed light on activation of coronavirus membrane fusion, which takes place through a receptor-driven ratcheting mechanism.

Unexpected Receptor Functional Mimicry Elucidates Activation of Coronavirus Fusion.,Walls AC, Xiong X, Park YJ, Tortorici MA, Snijder J, Quispe J, Cameroni E, Gopal R, Dai M, Lanzavecchia A, Zambon M, Rey FA, Corti D, Veesler D Cell. 2019 Jan 23. pii: S0092-8674(18)31642-8. doi: 10.1016/j.cell.2018.12.028. PMID:30712865^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Walls AC, Xiong X, Park YJ, Tortorici MA, Snijder J, Quispe J, Cameroni E, Gopal R, Dai M, Lanzavecchia A, Zambon M, Rey FA, Corti D, Veesler D. Unexpected Receptor Functional Mimicry Elucidates Activation of Coronavirus Fusion. Cell. 2019 Jan 23. pii: S0092-8674(18)31642-8. doi: 10.1016/j.cell.2018.12.028. PMID:30712865 doi:http://dx.doi.org/10.1016/j.cell.2018.12.028

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6nb6"

@@ Line 1: / Line 1: @@
 ==SARS-CoV complex with human neutralizing S230 antibody Fab fragment (state 1)==
-<StructureSection load='6nb6' size='340' side='right' caption='[[6nb6]], [[Resolution|resolution]] 4.20&Aring;' scene=''>
+<StructureSection load='6nb6' size='340' side='right'  caption='[[6nb6]], [[Resolution|resolution]] 4.20&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[6nb6]] is a 7 chain structure with sequence from [http://en.wikipedia.org/wiki/Cvhsa Cvhsa] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NB6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NB6 FirstGlance]. <br>

6nb6

From Proteopedia

Revision as of 08:32, 6 March 2019

SARS-CoV complex with human neutralizing S230 antibody Fab fragment (state 1)

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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