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| | ==Crystal structure of a TGEV coronavirus Spike fragment in complex with the TGEV neutralizing monoclonal antibody 1AF10== | | ==Crystal structure of a TGEV coronavirus Spike fragment in complex with the TGEV neutralizing monoclonal antibody 1AF10== |
| - | <StructureSection load='4f2m' size='340' side='right' caption='[[4f2m]], [[Resolution|resolution]] 3.00Å' scene=''> | + | <StructureSection load='4f2m' size='340' side='right'caption='[[4f2m]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4f2m]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice] and [http://en.wikipedia.org/wiki/Tgev_virulent_purdue Tgev virulent purdue]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4F2M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4F2M FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4f2m]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/TGEV_virulent_Purdue TGEV virulent Purdue]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4F2M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4F2M FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</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">X-ray diffraction, [[Resolution|Resolution]] 3Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4f5c|4f5c]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">S ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=398812 TGEV virulent Purdue])</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=4f2m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f2m OCA], [https://pdbe.org/4f2m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4f2m RCSB], [https://www.ebi.ac.uk/pdbsum/4f2m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4f2m ProSAT]</span></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=4f2m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f2m OCA], [http://pdbe.org/4f2m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4f2m RCSB], [http://www.ebi.ac.uk/pdbsum/4f2m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4f2m ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q0PKZ5_CVPPU Q0PKZ5_CVPPU] |
| | <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== |
| - | *[[3D structures of monoclonal antibody|3D structures of monoclonal antibody]] | + | *[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] |
| | + | *[[Spike protein 3D structures|Spike protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Tgev virulent purdue]] | + | [[Category: Mus musculus]] |
| - | [[Category: Casasnovas, J M]] | + | [[Category: TGEV virulent Purdue]] |
| - | [[Category: Enjuanes, L]] | + | [[Category: Casasnovas JM]] |
| - | [[Category: Mudgal, G]] | + | [[Category: Enjuanes L]] |
| - | [[Category: Ordono, D]] | + | [[Category: Mudgal G]] |
| - | [[Category: Reguera, J]] | + | [[Category: Ordono D]] |
| - | [[Category: Santiago, C]] | + | [[Category: Reguera J]] |
| - | [[Category: Aminopeptidase n]]
| + | [[Category: Santiago C]] |
| - | [[Category: Beta-barrel]]
| + | |
| - | [[Category: Cellular receptor]]
| + | |
| - | [[Category: Glycosylation]]
| + | |
| - | [[Category: Immunoglobulin]]
| + | |
| - | [[Category: Viral protein-immune system complex]]
| + | |
| - | [[Category: Virus entry]]
| + | |
| - | [[Category: Virus membrane]]
| + | |
| - | [[Category: Virus neutralization]]
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| Structural highlights
Function
Q0PKZ5_CVPPU
Publication Abstract from PubMed
The coronaviruses (CoVs) are enveloped viruses of animals and humans associated mostly with enteric and respiratory diseases, such as the severe acute respiratory syndrome and 10-20% of all common colds. A subset of CoVs uses the cell surface aminopeptidase N (APN), a membrane-bound metalloprotease, as a cell entry receptor. In these viruses, the envelope spike glycoprotein (S) mediates the attachment of the virus particles to APN and subsequent cell entry, which can be blocked by neutralizing antibodies. Here we describe the crystal structures of the receptor-binding domains (RBDs) of two closely related CoV strains, transmissible gastroenteritis virus (TGEV) and porcine respiratory CoV (PRCV), in complex with their receptor, porcine APN (pAPN), or with a neutralizing antibody. The data provide detailed information on the architecture of the dimeric pAPN ectodomain and its interaction with the CoV S. We show that a protruding receptor-binding edge in the S determines virus-binding specificity for recessed glycan-containing surfaces in the membrane-distal region of the pAPN ectodomain. Comparison of the RBDs of TGEV and PRCV to those of other related CoVs, suggests that the conformation of the S receptor-binding region determines cell entry receptor specificity. Moreover, the receptor-binding edge is a major antigenic determinant in the TGEV envelope S that is targeted by neutralizing antibodies. Our results provide a compelling view on CoV cell entry and immune neutralization, and may aid the design of antivirals or CoV vaccines. APN is also considered a target for cancer therapy and its structure, reported here, could facilitate the development of anti-cancer drugs.
Structural bases of coronavirus attachment to host aminopeptidase N and its inhibition by neutralizing antibodies.,Reguera J, Santiago C, Mudgal G, Ordono D, Enjuanes L, Casasnovas JM PLoS Pathog. 2012 Aug;8(8):e1002859. Epub 2012 Aug 2. PMID:22876187[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Reguera J, Santiago C, Mudgal G, Ordono D, Enjuanes L, Casasnovas JM. Structural bases of coronavirus attachment to host aminopeptidase N and its inhibition by neutralizing antibodies. PLoS Pathog. 2012 Aug;8(8):e1002859. Epub 2012 Aug 2. PMID:22876187 doi:10.1371/journal.ppat.1002859
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