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6u7e

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Revision as of 06:35, 6 May 2020

HCoV-229E RBD Class III in complex with human APN

Structural highlights

6u7e is a 4 chain structure with sequence from Cvh22 and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	6u7f, 6u7g, 6u7h
Gene:	ANPEP, APN, CD13, PEPN (HUMAN)
Activity:	Membrane alanyl aminopeptidase, with EC number 3.4.11.2
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[AMPN_HUMAN] Broad specificity aminopeptidase. Plays a role in the final digestion of peptides generated from hydrolysis of proteins by gastric and pancreatic proteases. May play a critical role in the pathogenesis of cholesterol gallstone disease. 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. Found to cleave antigen peptides bound to major histocompatibility complex class II molecules of presenting cells and to degrade neurotransmitters at synaptic junctions. Is also implicated as a regulator of IL-8 bioavailability in the endometrium, and therefore may contribute to the regulation of angiogenesis. Is used as a marker for acute myeloid leukemia and plays a role in tumor invasion. In case of human coronavirus 229E (HCoV-229E) infection, serves as receptor for HCoV-229E spike glycoprotein. Mediates as well human cytomegalovirus (HCMV) infection.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9]

Publication Abstract from PubMed

The coronavirus S-protein mediates receptor binding and fusion of the viral and host cell membranes. In HCoV-229E, its receptor binding domain (RBD) shows extensive sequence variation but how S-protein function is maintained is not understood. Reported are the X-ray crystal structures of Class III-V RBDs in complex with human aminopeptidase N (hAPN), as well as the electron cryomicroscopy structure of the 229E S-protein. The structures show that common core interactions define the specificity for hAPN and that the peripheral RBD sequence variation is accommodated by loop plasticity. The results provide insight into immune evasion and the cross-species transmission of 229E and related coronaviruses. We also find that the 229E S-protein can expose a portion of its helical core to solvent. This is undoubtedly facilitated by hydrophilic subunit interfaces that we show are conserved among coronaviruses. These interfaces likely play a role in the S-protein conformational changes associated with membrane fusion.

The human coronavirus HCoV-229E S-protein structure and receptor binding.,Li Z, Tomlinson ACA, Wong AHM, Zhou D, Desforges M, Talbot PJ, Benlekbir S, Rubinstein JL, Rini JM Elife. 2019 Oct 25;8. pii: 51230. doi: 10.7554/eLife.51230. PMID:31650956^[10]

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

References

↑ Yeager CL, Ashmun RA, Williams RK, Cardellichio CB, Shapiro LH, Look AT, Holmes KV. Human aminopeptidase N is a receptor for human coronavirus 229E. Nature. 1992 Jun 4;357(6377):420-2. PMID:1350662 doi:http://dx.doi.org/10.1038/357420a0
↑ Soderberg C, Giugni TD, Zaia JA, Larsson S, Wahlberg JM, Moller E. CD13 (human aminopeptidase N) mediates human cytomegalovirus infection. J Virol. 1993 Nov;67(11):6576-85. PMID:8105105
↑ Kolb AF, Maile J, Heister A, Siddell SG. Characterization of functional domains in the human coronavirus HCV 229E receptor. J Gen Virol. 1996 Oct;77 ( Pt 10):2515-21. PMID:8887485
↑ Noren K, Hansen GH, Clausen H, Noren O, Sjostrom H, Vogel LK. Defectively N-glycosylated and non-O-glycosylated aminopeptidase N (CD13) is normally expressed at the cell surface and has full enzymatic activity. Exp Cell Res. 1997 Feb 25;231(1):112-8. PMID:9056417 doi:10.1006/excr.1996.3455
↑ 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
↑ Dong X, An B, Salvucci Kierstead L, Storkus WJ, Amoscato AA, Salter RD. Modification of the amino terminus of a class II epitope confers resistance to degradation by CD13 on dendritic cells and enhances presentation to T cells. J Immunol. 2000 Jan 1;164(1):129-35. PMID:10605003
↑ Pasqualini R, Koivunen E, Kain R, Lahdenranta J, Sakamoto M, Stryhn A, Ashmun RA, Shapiro LH, Arap W, Ruoslahti E. Aminopeptidase N is a receptor for tumor-homing peptides and a target for inhibiting angiogenesis. Cancer Res. 2000 Feb 1;60(3):722-7. PMID:10676659
↑ Seli E, Senturk LM, Bahtiyar OM, Kayisli UA, Arici A. Expression of aminopeptidase N in human endometrium and regulation of its activity by estrogen. Fertil Steril. 2001 Jun;75(6):1172-6. PMID:11384645
↑ van Hensbergen Y, Broxterman HJ, Hanemaaijer R, Jorna AS, van Lent NA, Verheul HM, Pinedo HM, Hoekman K. Soluble aminopeptidase N/CD13 in malignant and nonmalignant effusions and intratumoral fluid. Clin Cancer Res. 2002 Dec;8(12):3747-54. PMID:12473585
↑ Li Z, Tomlinson ACA, Wong AHM, Zhou D, Desforges M, Talbot PJ, Benlekbir S, Rubinstein JL, Rini JM. The human coronavirus HCoV-229E S-protein structure and receptor binding. Elife. 2019 Oct 25;8. pii: 51230. doi: 10.7554/eLife.51230. PMID:31650956 doi:http://dx.doi.org/10.7554/eLife.51230

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/6u7e"

@@ Line 3: / Line 3: @@
 <StructureSection load='6u7e' size='340' side='right'caption='[[6u7e]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6u7e]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Cvh22 Cvh22] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6U7E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6U7E FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6u7e]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Cvh22 Cvh22] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6U7E OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6U7E FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</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=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">[[6u7f|6u7f]], [[6u7g|6u7g]], [[6u7h|6u7h]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ANPEP, APN, CD13, PEPN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6u7e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6u7e OCA], [http://pdbe.org/6u7e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6u7e RCSB], [http://www.ebi.ac.uk/pdbsum/6u7e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6u7e ProSAT]</span></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=6u7e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6u7e OCA], [http://pdbe.org/6u7e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6u7e RCSB], [http://www.ebi.ac.uk/pdbsum/6u7e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6u7e ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 21: / Line 21: @@
 </div>
 <div class="pdbe-citations 6u7e" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Sandbox 3001|Sandbox 3001]]
+*[[Spike protein|Spike protein]]
 == References ==
 <references/>

6u7e

From Proteopedia

Revision as of 06:35, 6 May 2020

HCoV-229E RBD Class III in complex with human APN

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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