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6pz8

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Revision as of 12:36, 18 December 2019

MERS S0 trimer in complex with variable domain of antibody G2

Structural highlights

6pz8 is a 12 chain structure with sequence from Lk3 transgenic mice and Mers. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[W6A090_9BETC] Spike protein S1: attaches the virion to the cell membrane by interacting with host receptor, initiating the infection.[HAMAP-Rule:MF_04099] Spike protein S2': Acts as a viral fusion peptide which is unmasked following S2 cleavage occurring upon virus endocytosis.[HAMAP-Rule:MF_04099] Spike protein S2: 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]

Publication Abstract from PubMed

Middle East respiratory syndrome coronavirus (MERS-CoV) emerged into the human population in 2012 and has caused substantial morbidity and mortality. Potently neutralizing antibodies targeting the receptor-binding domain (RBD) on MERS-CoV spike (S) protein have been characterized, but much less is known about antibodies targeting non-RBD epitopes. Here, we report the structural and functional characterization of G2, a neutralizing antibody targeting the MERS-CoV S1 N-terminal domain (S1-NTD). Structures of G2 alone and in complex with the MERS-CoV S1-NTD define a site of vulnerability comprising two loops, each of which contain a residue mutated in G2-escape variants. Cell-surface binding studies and in vitro competition experiments demonstrate that G2 strongly disrupts the attachment of MERS-CoV S to its receptor, dipeptidyl peptidase-4 (DPP4), with the inhibition requiring the native trimeric S conformation. These results advance our understanding of antibody-mediated neutralization of coronaviruses and should facilitate the development of immunotherapeutics and vaccines against MERS-CoV.

Structural Definition of a Neutralization-Sensitive Epitope on the MERS-CoV S1-NTD.,Wang N, Rosen O, Wang L, Turner HL, Stevens LJ, Corbett KS, Bowman CA, Pallesen J, Shi W, Zhang Y, Leung K, Kirchdoerfer RN, Becker MM, Denison MR, Chappell JD, Ward AB, Graham BS, McLellan JS Cell Rep. 2019 Sep 24;28(13):3395-3405.e6. doi: 10.1016/j.celrep.2019.08.052. PMID:31553909^[1]

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

References

↑ Wang N, Rosen O, Wang L, Turner HL, Stevens LJ, Corbett KS, Bowman CA, Pallesen J, Shi W, Zhang Y, Leung K, Kirchdoerfer RN, Becker MM, Denison MR, Chappell JD, Ward AB, Graham BS, McLellan JS. Structural Definition of a Neutralization-Sensitive Epitope on the MERS-CoV S1-NTD. Cell Rep. 2019 Sep 24;28(13):3395-3405.e6. doi: 10.1016/j.celrep.2019.08.052. PMID:31553909 doi:http://dx.doi.org/10.1016/j.celrep.2019.08.052

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/6pz8"

@@ Line 3: / Line 3: @@
 <StructureSection load='6pz8' size='340' side='right'caption='[[6pz8]], [[Resolution|resolution]] 4.19&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6pz8]] is a 12 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PZ8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6PZ8 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6pz8]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice] and [http://en.wikipedia.org/wiki/Mers Mers]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PZ8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6PZ8 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>
 <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=6pz8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pz8 OCA], [http://pdbe.org/6pz8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pz8 RCSB], [http://www.ebi.ac.uk/pdbsum/6pz8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pz8 ProSAT]</span></td></tr>
@@ Line 23: / Line 23: @@
 </StructureSection>
 [[Category: Large Structures]]
+[[Category: Lk3 transgenic mice]]
+[[Category: Mers]]
 [[Category: Bowman, C A]]
 [[Category: Pallesen, J]]

6pz8

From Proteopedia

Revision as of 12:36, 18 December 2019

MERS S0 trimer in complex with variable domain of antibody G2

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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