4f5c: Difference between revisions
New page: '''Unreleased structure''' The entry 4f5c is ON HOLD Authors: Santiago, C., Reguera, J., Gaurav, M., Ordono, D., Enjuanes, L., Casasnovas, J.M. Description: Crystal structure of the sp... |
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The entry | ==Crystal structure of the spike receptor binding domain of a porcine respiratory coronavirus in complex with the pig aminopeptidase N ectodomain== | ||
<StructureSection load='4f5c' size='340' side='right'caption='[[4f5c]], [[Resolution|resolution]] 3.20Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4f5c]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Porcine_respiratory_coronavirus Porcine respiratory coronavirus] and [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4F5C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4F5C FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.2Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=4f5c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f5c OCA], [https://pdbe.org/4f5c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4f5c RCSB], [https://www.ebi.ac.uk/pdbsum/4f5c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4f5c ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/AMPN_PIG AMPN_PIG] Broad specificity aminopeptidase. Plays a role in the final digestion of peptides generated from hydrolysis of proteins by gastric and pancreatic proteases. May be involved in the metabolism of regulatory peptides of diverse cell types, responsible for the processing of peptide hormones, such as angiotensin III and IV, neuropeptides, and chemokines and involved the cleavage of peptides bound to major histocompatibility complex class II molecules of antigen presenting cells. May have a role in angiogenesis (By similarity). It is able to degrade Leu-enkephalin and Met-enkephalin but not cholecystokinin CCK8, neuromedin C (GRP-10), somatostatin-14, substance P and vasoactive intestinal peptide. In case of porcine transmissible gastroenteritis coronavirus (TGEV) and porcine respiratory coronavirus (PRCoV) infections, serves as a receptor for TGEV and PRCoV spike glycoprotein in a species-specific manner.<ref>PMID:7913510</ref> <ref>PMID:1350661</ref> <ref>PMID:7911642</ref> <ref>PMID:8985407</ref> <ref>PMID:9634079</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:22876187</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4f5c" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Aminopeptidase 3D structures|Aminopeptidase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Porcine respiratory coronavirus]] | |||
[[Category: Sus scrofa]] | |||
[[Category: Casasnovas JM]] | |||
[[Category: Enjuanes L]] | |||
[[Category: Gaurav M]] | |||
[[Category: Ordono D]] | |||
[[Category: Reguera J]] | |||
[[Category: Santiago C]] | |||
Latest revision as of 11:20, 9 October 2024
Structural highlights
FunctionAMPN_PIG Broad specificity aminopeptidase. Plays a role in the final digestion of peptides generated from hydrolysis of proteins by gastric and pancreatic proteases. May be involved in the metabolism of regulatory peptides of diverse cell types, responsible for the processing of peptide hormones, such as angiotensin III and IV, neuropeptides, and chemokines and involved the cleavage of peptides bound to major histocompatibility complex class II molecules of antigen presenting cells. May have a role in angiogenesis (By similarity). It is able to degrade Leu-enkephalin and Met-enkephalin but not cholecystokinin CCK8, neuromedin C (GRP-10), somatostatin-14, substance P and vasoactive intestinal peptide. In case of porcine transmissible gastroenteritis coronavirus (TGEV) and porcine respiratory coronavirus (PRCoV) infections, serves as a receptor for TGEV and PRCoV spike glycoprotein in a species-specific manner.[1] [2] [3] [4] [5] Publication Abstract from PubMedThe 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[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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