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| | <SX load='6pz8' size='340' side='right' viewer='molstar' caption='[[6pz8]], [[Resolution|resolution]] 4.19Å' scene=''> | | <SX load='6pz8' size='340' side='right' viewer='molstar' caption='[[6pz8]], [[Resolution|resolution]] 4.19Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <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://proteopedia.org/fgij/fg.htm?mol=6PZ8 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6pz8]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Middle_East_respiratory_syndrome-related_coronavirus Middle East respiratory syndrome-related coronavirus] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. 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 [https://proteopedia.org/fgij/fg.htm?mol=6PZ8 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.19Å</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=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> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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'>[https://proteopedia.org/fgij/fg.htm?mol=6pz8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pz8 OCA], [https://pdbe.org/6pz8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6pz8 RCSB], [https://www.ebi.ac.uk/pdbsum/6pz8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6pz8 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/W6A090_9BETC 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] | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Spike protein|Spike protein]] | + | *[[Antibody 3D structures|Antibody 3D structures]] |
| | + | *[[Sandbox 3001|Sandbox 3001]] |
| | + | *[[Spike protein 3D structures|Spike protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </SX> | | </SX> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Middle East respiratory syndrome-related coronavirus]] |
| - | [[Category: Mers]] | + | [[Category: Mus musculus]] |
| - | [[Category: Bowman, C A]] | + | [[Category: Bowman CA]] |
| - | [[Category: Pallesen, J]] | + | [[Category: Pallesen J]] |
| - | [[Category: Ward, A B]] | + | [[Category: Ward AB]] |
| - | [[Category: Coronavirus]]
| + | |
| - | [[Category: Dpp4]]
| + | |
| - | [[Category: Membrane fusion]]
| + | |
| - | [[Category: Mers-cov]]
| + | |
| - | [[Category: Receptor-binding]]
| + | |
| - | [[Category: Viral protein-immune system complex]]
| + | |
| Structural highlights
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
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
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
- ↑ 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
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