6atk

From Proteopedia

(Difference between revisions)

Revision as of 07:23, 6 December 2017

Crystal structure of the human coronavirus 229E spike protein receptor binding domain in complex with human aminopeptidase N

Structural highlights

6atk is a 6 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
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] [SPIKE_CVH22] S1 region attaches the virion to the cell membrane by interacting with human ANPEP/aminopeptidase N, initiating the infection. Binding to the receptor probably induces conformational changes in the S glycoprotein unmasking the fusion peptide of S2 region and activating membranes fusion. S2 region belongs to the class I viral fusion protein. Under the current model, the protein has at least 3 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) regions 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 (By similarity).

Publication Abstract from PubMed

RNA viruses are characterized by a high mutation rate, a buffer against environmental change. Nevertheless, the means by which random mutation improves viral fitness is not well characterized. Here we report the X-ray crystal structure of the receptor-binding domain (RBD) of the human coronavirus, HCoV-229E, in complex with the ectodomain of its receptor, aminopeptidase N (APN). Three extended loops are solely responsible for receptor binding and the evolution of HCoV-229E and its close relatives is accompanied by changing loop-receptor interactions. Phylogenetic analysis shows that the natural HCoV-229E receptor-binding loop variation observed defines six RBD classes whose viruses have successively replaced each other in the human population over the past 50 years. These RBD classes differ in their affinity for APN and their ability to bind an HCoV-229E neutralizing antibody. Together, our results provide a model for alphacoronavirus adaptation and evolution based on the use of extended loops for receptor binding.

Receptor-binding loops in alphacoronavirus adaptation and evolution.,Wong AHM, Tomlinson ACA, Zhou D, Satkunarajah M, Chen K, Sharon C, Desforges M, Talbot PJ, Rini JM Nat Commun. 2017 Nov 23;8(1):1735. doi: 10.1038/s41467-017-01706-x. PMID:29170370^[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
↑ Wong AHM, Tomlinson ACA, Zhou D, Satkunarajah M, Chen K, Sharon C, Desforges M, Talbot PJ, Rini JM. Receptor-binding loops in alphacoronavirus adaptation and evolution. Nat Commun. 2017 Nov 23;8(1):1735. doi: 10.1038/s41467-017-01706-x. PMID:29170370 doi:http://dx.doi.org/10.1038/s41467-017-01706-x

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6atk"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6atk is ON HOLD  until Paper Publication
+==Crystal structure of the human coronavirus 229E spike protein receptor binding domain in complex with human aminopeptidase N==
+<StructureSection load='6atk' size='340' side='right' caption='[[6atk]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6atk]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ATK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ATK 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='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=6atk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6atk OCA], [http://pdbe.org/6atk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6atk RCSB], [http://www.ebi.ac.uk/pdbsum/6atk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6atk ProSAT]</span></td></tr>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/AMPN_HUMAN 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.<ref>PMID:1350662</ref> <ref>PMID:8105105</ref> <ref>PMID:8887485</ref> <ref>PMID:9056417</ref> <ref>PMID:9634079</ref> <ref>PMID:10605003</ref> <ref>PMID:10676659</ref> <ref>PMID:11384645</ref> <ref>PMID:12473585</ref>  [[http://www.uniprot.org/uniprot/SPIKE_CVH22 SPIKE_CVH22]] S1 region attaches the virion to the cell membrane by interacting with human ANPEP/aminopeptidase N, initiating the infection. Binding to the receptor probably induces conformational changes in the S glycoprotein unmasking the fusion peptide of S2 region and activating membranes fusion. S2 region belongs to the class I viral fusion protein. Under the current model, the protein has at least 3 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) regions 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 (By similarity).
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+RNA viruses are characterized by a high mutation rate, a buffer against environmental change. Nevertheless, the means by which random mutation improves viral fitness is not well characterized. Here we report the X-ray crystal structure of the receptor-binding domain (RBD) of the human coronavirus, HCoV-229E, in complex with the ectodomain of its receptor, aminopeptidase N (APN). Three extended loops are solely responsible for receptor binding and the evolution of HCoV-229E and its close relatives is accompanied by changing loop-receptor interactions. Phylogenetic analysis shows that the natural HCoV-229E receptor-binding loop variation observed defines six RBD classes whose viruses have successively replaced each other in the human population over the past 50 years. These RBD classes differ in their affinity for APN and their ability to bind an HCoV-229E neutralizing antibody. Together, our results provide a model for alphacoronavirus adaptation and evolution based on the use of extended loops for receptor binding.
-Authors:
+Receptor-binding loops in alphacoronavirus adaptation and evolution.,Wong AHM, Tomlinson ACA, Zhou D, Satkunarajah M, Chen K, Sharon C, Desforges M, Talbot PJ, Rini JM Nat Commun. 2017 Nov 23;8(1):1735. doi: 10.1038/s41467-017-01706-x. PMID:29170370<ref>PMID:29170370</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 6atk" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Membrane alanyl aminopeptidase]]
+[[Category: Rini, J M]]
+[[Category: Wong, A H]]
+[[Category: Coronavirus]]
+[[Category: Hydrolase-viral protein complex]]
+[[Category: Receptor]]
+[[Category: Spike]]

6atk

From Proteopedia

Revision as of 07:23, 6 December 2017

Crystal structure of the human coronavirus 229E spike protein receptor binding domain in complex with human aminopeptidase N

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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