View source for 6atk


==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 with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_coronavirus_229E Human coronavirus 229E]. 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 [https://proteopedia.org/fgij/fg.htm?mol=6ATK 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]] 3.505&#8491;</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=6atk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6atk OCA], [https://pdbe.org/6atk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6atk RCSB], [https://www.ebi.ac.uk/pdbsum/6atk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6atk ProSAT]</span></td></tr>
</table>
== Function ==
[https://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> 
<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.

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>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6atk" style="background-color:#fffaf0;"></div>

==See Also==
*[[Sandbox 3001|Sandbox 3001]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Human coronavirus 229E]]
[[Category: Large Structures]]
[[Category: Rini JM]]
[[Category: Wong AH]]