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5zxv

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Structural definition of a unique neutralization epitope on the receptor-binding domain of MERS-CoV spike glycoprotein

Structural highlights

5zxv is a 6 chain structure with sequence from Homo sapiens and Middle East respiratory syndrome-related coronavirus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 4.482Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SPIKE_MERS1 Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection (By similarity). Interacts with host DPP4 to mediate virla entry.[HAMAP-Rule:MF_04099]^[1] 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]

Publication Abstract from PubMed

The major mechanism of antibody-mediated neutralization of the Middle East respiratory syndrome coronavirus (MERS-CoV) involves competition with the cellular receptor dipeptidyl peptidase 4 (DPP4) for binding to the receptor-binding domain (RBD) of the spike (S) glycoprotein. Here, we report a unique epitope and unusual neutralizing mechanism of the isolated human antibody MERS-4. Structurally, MERS-4 approached the RBD from the outside of the RBD-DPP4 binding interface. Such binding resulted in the folding of the beta5-beta6 loop toward a shallow groove on the RBD interface critical for accommodating DPP4. The key residues for binding are identified through site-directed mutagenesis. Structural modeling revealed that MERS-4 binds to RBD only in the "up" position in the S trimer. Furthermore, MERS-4 demonstrated synergy with several reported antibodies. These results indicate that MERS-4 neutralizes MERS-CoV by indirect rather than direct competition with DPP4. This mechanism provides a valuable addition for the combined use of antibodies against MERS-CoV infection.

Structural Definition of a Unique Neutralization Epitope on the Receptor-Binding Domain of MERS-CoV Spike Glycoprotein.,Zhang S, Zhou P, Wang P, Li Y, Jiang L, Jia W, Wang H, Fan A, Wang D, Shi X, Fang X, Hammel M, Wang S, Wang X, Zhang L Cell Rep. 2018 Jul 10;24(2):441-452. doi: 10.1016/j.celrep.2018.06.041. PMID:29996104^[2]

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

References

↑ Raj VS, Mou H, Smits SL, Dekkers DH, Muller MA, Dijkman R, Muth D, Demmers JA, Zaki A, Fouchier RA, Thiel V, Drosten C, Rottier PJ, Osterhaus AD, Bosch BJ, Haagmans BL. Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature. 2013 Mar 14;495(7440):251-4. doi: 10.1038/nature12005. PMID:23486063 doi:http://dx.doi.org/10.1038/nature12005
↑ Zhang S, Zhou P, Wang P, Li Y, Jiang L, Jia W, Wang H, Fan A, Wang D, Shi X, Fang X, Hammel M, Wang S, Wang X, Zhang L. Structural Definition of a Unique Neutralization Epitope on the Receptor-Binding Domain of MERS-CoV Spike Glycoprotein. Cell Rep. 2018 Jul 10;24(2):441-452. doi: 10.1016/j.celrep.2018.06.041. PMID:29996104 doi:http://dx.doi.org/10.1016/j.celrep.2018.06.041

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5zxv"

Categories: Homo sapiens | Large Structures | Middle East respiratory syndrome-related coronavirus | Wang X | Zhang S

@@ Line 3: / Line 3: @@
 <StructureSection load='5zxv' size='340' side='right'caption='[[5zxv]], [[Resolution|resolution]] 4.48&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5zxv]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZXV OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5ZXV FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5zxv]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Middle_East_respiratory_syndrome-related_coronavirus Middle East respiratory syndrome-related coronavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZXV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ZXV 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=5zxv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zxv OCA], [http://pdbe.org/5zxv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zxv RCSB], [http://www.ebi.ac.uk/pdbsum/5zxv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zxv ProSAT]</span></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 4.482&#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=5zxv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zxv OCA], [https://pdbe.org/5zxv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5zxv RCSB], [https://www.ebi.ac.uk/pdbsum/5zxv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5zxv ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/SPIKE_MERS1 SPIKE_MERS1] Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection (By similarity). Interacts with host DPP4 to mediate virla entry.[HAMAP-Rule:MF_04099]<ref>PMID:23486063</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 ==
@@ Line 23: / Line 26: @@
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Wang, X]]
+[[Category: Middle East respiratory syndrome-related coronavirus]]
-[[Category: Zhang, S]]
+[[Category: Wang X]]
-[[Category: Antibody]]
+[[Category: Zhang S]]
-[[Category: Viral protein]]

5zxv

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Current revision

Structural definition of a unique neutralization epitope on the receptor-binding domain of MERS-CoV spike glycoprotein

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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