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3kbh
From Proteopedia
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| - | {{Seed}} | ||
| - | [[Image:3kbh.jpg|left|200px]] | ||
| - | < | + | ==Crystal structure of NL63 respiratory coronavirus receptor-binding domain complexed with its human receptor== |
| - | + | <StructureSection load='3kbh' size='340' side='right' caption='[[3kbh]], [[Resolution|resolution]] 3.31Å' scene=''> | |
| - | + | == Structural highlights == | |
| - | + | <table><tr><td colspan='2'>[[3kbh]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Cvhnl Cvhnl] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KBH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KBH 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></td></tr> | |
| - | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2ajf|2ajf]]</td></tr> | |
| - | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ACE2, spike protein, UNQ868/PRO1885 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), 2, human angiotensin-converting enzyme 2, S ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=277944 CVHNL])</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=3kbh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kbh OCA], [http://pdbe.org/3kbh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3kbh RCSB], [http://www.ebi.ac.uk/pdbsum/3kbh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3kbh ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/ACE2_HUMAN ACE2_HUMAN]] Carboxypeptidase which converts angiotensin I to angiotensin 1-9, a peptide of unknown function, and angiotensin II to angiotensin 1-7, a vasodilator. Also able to hydrolyze apelin-13 and dynorphin-13 with high efficiency. May be an important regulator of heart function. In case of human coronaviruses SARS and HCoV-NL63 infections, serve as functional receptor for the spike glycoprotein of both coronaviruses.<ref>PMID:10969042</ref> <ref>PMID:10924499</ref> <ref>PMID:14647384</ref> [[http://www.uniprot.org/uniprot/SPIKE_CVHNL SPIKE_CVHNL]] S1 region attaches the virion to the cell membrane by interacting with human ACE2, 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). | ||
| + | == Evolutionary Conservation == | ||
| + | [[Image:Consurf_key_small.gif|200px|right]] | ||
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kb/3kbh_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </jmolCheckbox> | ||
| + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3kbh ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | NL63 coronavirus (NL63-CoV), a prevalent human respiratory virus, is the only group I coronavirus known to use angiotensin-converting enzyme 2 (ACE2) as its receptor. Incidentally, ACE2 is also used by group II SARS coronavirus (SARS-CoV). We investigated how different groups of coronaviruses recognize the same receptor, whereas homologous group I coronaviruses recognize different receptors. We determined the crystal structure of NL63-CoV spike protein receptor-binding domain (RBD) complexed with human ACE2. NL63-CoV RBD has a novel beta-sandwich core structure consisting of 2 layers of beta-sheets, presenting 3 discontinuous receptor-binding motifs (RBMs) to bind ACE2. NL63-CoV and SARS-CoV have no structural homology in RBD cores or RBMs; yet the 2 viruses recognize common ACE2 regions, largely because of a "virus-binding hotspot" on ACE2. Among group I coronaviruses, RBD cores are conserved but RBMs are variable, explaining how these viruses recognize different receptors. These results provide a structural basis for understanding viral evolution and virus-receptor interactions. | ||
| - | + | Crystal structure of NL63 respiratory coronavirus receptor-binding domain complexed with its human receptor.,Wu K, Li W, Peng G, Li F Proc Natl Acad Sci U S A. 2009 Nov 24;106(47):19970-4. Epub 2009 Nov 9. PMID:19901337<ref>PMID:19901337</ref> | |
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 3kbh" style="background-color:#fffaf0;"></div> | ||
| - | + | ==See Also== | |
| - | + | *[[Angiotensin-Converting Enzyme|Angiotensin-Converting Enzyme]] | |
| - | + | == References == | |
| - | + | <references/> | |
| - | + | __TOC__ | |
| - | + | </StructureSection> | |
| - | == | + | [[Category: Cvhnl]] |
| - | + | [[Category: Human]] | |
| - | + | [[Category: Li, F]] | |
| - | == | + | [[Category: Li, W]] |
| - | < | + | [[Category: Peng, G]] |
| - | [[Category: | + | [[Category: Wu, K]] |
| - | [[Category: Human | + | |
| - | [[Category: Li, F | + | |
| - | [[Category: Li, W | + | |
| - | [[Category: Peng, G | + | |
| - | [[Category: Wu, K | + | |
| - | + | ||
[[Category: Beta sandwich]] | [[Category: Beta sandwich]] | ||
[[Category: Carboxypeptidase]] | [[Category: Carboxypeptidase]] | ||
[[Category: Cell membrane]] | [[Category: Cell membrane]] | ||
[[Category: Chloride]] | [[Category: Chloride]] | ||
| - | [[Category: Coiled coil]] | ||
[[Category: Envelope protein]] | [[Category: Envelope protein]] | ||
[[Category: Fusion protein]] | [[Category: Fusion protein]] | ||
[[Category: Glycoprotein]] | [[Category: Glycoprotein]] | ||
[[Category: Host-virus interaction]] | [[Category: Host-virus interaction]] | ||
| + | [[Category: Hydrolase]] | ||
[[Category: Membrane]] | [[Category: Membrane]] | ||
[[Category: Metal-binding]] | [[Category: Metal-binding]] | ||
[[Category: Metalloprotease]] | [[Category: Metalloprotease]] | ||
| - | [[Category: Polymorphism]] | ||
[[Category: Protease]] | [[Category: Protease]] | ||
[[Category: Secreted]] | [[Category: Secreted]] | ||
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[[Category: Virion]] | [[Category: Virion]] | ||
[[Category: Virulence]] | [[Category: Virulence]] | ||
| - | |||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Dec 16 13:02:38 2009'' | ||
Current revision
Crystal structure of NL63 respiratory coronavirus receptor-binding domain complexed with its human receptor
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Categories: Cvhnl | Human | Li, F | Li, W | Peng, G | Wu, K | Beta sandwich | Carboxypeptidase | Cell membrane | Chloride | Envelope protein | Fusion protein | Glycoprotein | Host-virus interaction | Hydrolase | Membrane | Metal-binding | Metalloprotease | Protease | Secreted | Transmembrane | Virion | Virulence

