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| | == Structural highlights == | | == Structural highlights == |
| | <table><tr><td colspan='2'>[[1p6a]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Human_adenovirus_12 Human adenovirus 12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1P6A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1P6A FirstGlance]. <br> | | <table><tr><td colspan='2'>[[1p6a]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Human_adenovirus_12 Human adenovirus 12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1P6A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1P6A FirstGlance]. <br> |
| - | </td></tr><tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1kac|1kac]], [[1p69|1p69]]</td></tr> | + | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1kac|1kac]], [[1p69|1p69]]</td></tr> |
| - | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1p6a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1p6a OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1p6a RCSB], [http://www.ebi.ac.uk/pdbsum/1p6a 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=1p6a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1p6a OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1p6a RCSB], [http://www.ebi.ac.uk/pdbsum/1p6a PDBsum]</span></td></tr> |
| - | <table> | + | </table> |
| | + | == Function == |
| | + | [[http://www.uniprot.org/uniprot/CXAR_HUMAN CXAR_HUMAN]] Component of the epithelial apical junction complex that is essential for the tight junction integrity. Proposed to function as a homophilic cell adhesion molecule. Recruits MPDZ to intercellular contact sites. Probably involved in transepithelial migration of polymorphonuclear leukocytes (PMN) through adhesive interactions with AMICA1/JAML located in the plasma membrane of PMN.<ref>PMID:9096397</ref> <ref>PMID:11734628</ref> <ref>PMID:12297051</ref> <ref>PMID:15800062</ref> [[http://www.uniprot.org/uniprot/SPIKE_ADE12 SPIKE_ADE12]] Forms spikes that protrude from each vertex of the icosahedral capsid. Interacts with host receptor CXCAR to provide virion initial attachment to target cell. Fiber proteins are shed during virus entry, when virus is still at the cell surface (By similarity). |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| | [[Category: Human adenovirus 12]] | | [[Category: Human adenovirus 12]] |
| - | [[Category: Bewley, M C.]] | + | [[Category: Bewley, M C]] |
| - | [[Category: Flanagan, J M.]] | + | [[Category: Flanagan, J M]] |
| - | [[Category: Freimuth, P.]] | + | [[Category: Freimuth, P]] |
| - | [[Category: Graziano, V.]] | + | [[Category: Graziano, V]] |
| - | [[Category: Howitt, J.]] | + | [[Category: Howitt, J]] |
| | [[Category: Viral protein]] | | [[Category: Viral protein]] |
| | [[Category: Viral protein-receptor complex]] | | [[Category: Viral protein-receptor complex]] |
| | [[Category: Virus]] | | [[Category: Virus]] |
| Structural highlights
Function
[CXAR_HUMAN] Component of the epithelial apical junction complex that is essential for the tight junction integrity. Proposed to function as a homophilic cell adhesion molecule. Recruits MPDZ to intercellular contact sites. Probably involved in transepithelial migration of polymorphonuclear leukocytes (PMN) through adhesive interactions with AMICA1/JAML located in the plasma membrane of PMN.[1] [2] [3] [4] [SPIKE_ADE12] Forms spikes that protrude from each vertex of the icosahedral capsid. Interacts with host receptor CXCAR to provide virion initial attachment to target cell. Fiber proteins are shed during virus entry, when virus is still at the cell surface (By similarity).
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The majority of adenovirus serotypes can bind to the coxsackievirus and adenovirus receptor (CAR) on human cells despite only limited conservation of the amino acid residues that comprise the receptor-binding sites of these viruses. Using a fluorescence anisotropy-based assay, we determined that the recombinant knob domain of the fiber protein from adenovirus serotype (Ad) 2 binds the soluble, N-terminal domain (domain 1 (D1)) of CAR with 8-fold greater affinity than does the recombinant knob domain from Ad12. Homology modeling predicted that the increased affinity of Ad2 knob for CAR D1 could result from additional contacts within the binding interface contributed by two residues, Ser408 and Tyr477, which are not conserved in the Ad12 knob. Consistent with this structural model, substitution of serine and tyrosine for the corresponding residues in the Ad12 knob (P417S and S489Y) increased the binding affinity by 4- and 8-fold, respectively, whereas the double mutation increased binding affinity 10-fold. X-ray structure analysis of Ad12 knob mutants P417S and S489Y indicated that both substituted residues potentially could form additional hydrogen bonds across the knob-CAR interface. Structural changes resulting from these mutations were highly localized, implying that the high tolerance for surface variation conferred by the stable knob scaffold can minimize the impact of antigenic drift on binding specificity and affinity during evolution of virus serotypes. Our results suggest that the interaction of knob domains from different adenovirus serotypes with CAR D1 can be accurately modeled using the Ad12 knob-CAR D1 crystal structure as a template.
Structural basis for variation in adenovirus affinity for the cellular coxsackievirus and adenovirus receptor.,Howitt J, Bewley MC, Graziano V, Flanagan JM, Freimuth P J Biol Chem. 2003 Jul 11;278(28):26208-15. Epub 2003 Apr 25. PMID:12716886[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Tomko RP, Xu R, Philipson L. HCAR and MCAR: the human and mouse cellular receptors for subgroup C adenoviruses and group B coxsackieviruses. Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3352-6. PMID:9096397
- ↑ Cohen CJ, Shieh JT, Pickles RJ, Okegawa T, Hsieh JT, Bergelson JM. The coxsackievirus and adenovirus receptor is a transmembrane component of the tight junction. Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):15191-6. Epub 2001 Dec 4. PMID:11734628 doi:10.1073/pnas.261452898
- ↑ Walters RW, Freimuth P, Moninger TO, Ganske I, Zabner J, Welsh MJ. Adenovirus fiber disrupts CAR-mediated intercellular adhesion allowing virus escape. Cell. 2002 Sep 20;110(6):789-99. PMID:12297051
- ↑ Zen K, Liu Y, McCall IC, Wu T, Lee W, Babbin BA, Nusrat A, Parkos CA. Neutrophil migration across tight junctions is mediated by adhesive interactions between epithelial coxsackie and adenovirus receptor and a junctional adhesion molecule-like protein on neutrophils. Mol Biol Cell. 2005 Jun;16(6):2694-703. Epub 2005 Mar 30. PMID:15800062 doi:E05-01-0036
- ↑ Howitt J, Bewley MC, Graziano V, Flanagan JM, Freimuth P. Structural basis for variation in adenovirus affinity for the cellular coxsackievirus and adenovirus receptor. J Biol Chem. 2003 Jul 11;278(28):26208-15. Epub 2003 Apr 25. PMID:12716886 doi:http://dx.doi.org/10.1074/jbc.M301492200
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