4f5c

From Proteopedia

(Difference between revisions)

Revision as of 12:25, 11 August 2016

Crystal structure of the spike receptor binding domain of a porcine respiratory coronavirus in complex with the pig aminopeptidase N ectodomain

Structural highlights

4f5c is a 4 chain structure with sequence from Pig and Porcine respiratory coronavirus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	4f2m
Gene:	ANPEP (PIG)
Activity:	Membrane alanyl aminopeptidase, with EC number 3.4.11.2
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2] ^[3] ^[4] ^[5]

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^[6]

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

References

↑ Delmas B, Gelfi J, Kut E, Sjostrom H, Noren O, Laude H. Determinants essential for the transmissible gastroenteritis virus-receptor interaction reside within a domain of aminopeptidase-N that is distinct from the enzymatic site. J Virol. 1994 Aug;68(8):5216-24. PMID:7913510
↑ Delmas B, Gelfi J, L'Haridon R, Vogel LK, Sjostrom H, Noren O, Laude H. Aminopeptidase N is a major receptor for the entero-pathogenic coronavirus TGEV. Nature. 1992 Jun 4;357(6377):417-20. PMID:1350661 doi:http://dx.doi.org/10.1038/357417a0
↑ Delmas B, Gelfi J, Sjostrom H, Noren O, Laude H. Further characterization of aminopeptidase-N as a receptor for coronaviruses. Adv Exp Med Biol. 1993;342:293-8. PMID:7911642
↑ Benbacer L, Kut E, Besnardeau L, Laude H, Delmas B. Interspecies aminopeptidase-N chimeras reveal species-specific receptor recognition by canine coronavirus, feline infectious peritonitis virus, and transmissible gastroenteritis virus. J Virol. 1997 Jan;71(1):734-7. PMID:8985407
↑ Hegyi A, Kolb AF. Characterization of determinants involved in the feline infectious peritonitis virus receptor function of feline aminopeptidase N. J Gen Virol. 1998 Jun;79 ( Pt 6):1387-91. PMID:9634079
↑ 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

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/4f5c"

@@ Line 1: / Line 1: @@
 ==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]] 3.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4f5c]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Porcine_respiratory_coronavirus Porcine respiratory coronavirus] and [http://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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4F5C FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4f5c]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Pig Pig] and [http://en.wikipedia.org/wiki/Porcine_respiratory_coronavirus Porcine respiratory coronavirus]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4F5C FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4f2m|4f2m]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ANPEP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9823 Sus scrofa])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ANPEP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9823 PIG])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Membrane_alanyl_aminopeptidase Membrane alanyl aminopeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.11.2 3.4.11.2] </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=4f5c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f5c OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4f5c RCSB], [http://www.ebi.ac.uk/pdbsum/4f5c PDBsum]</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=4f5c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f5c OCA], [http://pdbe.org/4f5c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4f5c RCSB], [http://www.ebi.ac.uk/pdbsum/4f5c PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4f5c ProSAT]</span></td></tr>
 </table>
+== Function ==
+[[http://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 ==
@@ Line 17: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4f5c" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 25: / Line 29: @@
 </StructureSection>
 [[Category: Membrane alanyl aminopeptidase]]
+[[Category: Pig]]
 [[Category: Porcine respiratory coronavirus]]
-[[Category: Sus scrofa]]
 [[Category: Casasnovas, J M]]
 [[Category: Enjuanes, L]]

4f5c

From Proteopedia

Revision as of 12:25, 11 August 2016

Crystal structure of the spike receptor binding domain of a porcine respiratory coronavirus in complex with the pig aminopeptidase N ectodomain

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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