1p6a

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[[Image:1p6a.gif|left|200px]]
 
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{{Structure
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==STRUCTURAL BASIS FOR VARIATION IN ADENOVIRUS AFFINITY FOR THE CELLULAR RECEPTOR CAR (S489Y MUTANT)==
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|PDB= 1p6a |SIZE=350|CAPTION= <scene name='initialview01'>1p6a</scene>, resolution 2.90&Aring;
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<StructureSection load='1p6a' size='340' side='right'caption='[[1p6a]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND=
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<table><tr><td colspan='2'>[[1p6a]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://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 [https://proteopedia.org/fgij/fg.htm?mol=1P6A FirstGlance]. <br>
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|ACTIVITY=
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.9&#8491;</td></tr>
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|GENE=
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1p6a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1p6a OCA], [https://pdbe.org/1p6a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1p6a RCSB], [https://www.ebi.ac.uk/pdbsum/1p6a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1p6a ProSAT]</span></td></tr>
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}}
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</table>
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== Function ==
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'''STRUCTURAL BASIS FOR VARIATION IN ASDENOVIRUS AFFINITY FOR THE CELLULAR RECEPTOR CAR (S489Y MUTANT)'''
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[https://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).
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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==Overview==
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Check<jmol>
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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.
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/p6/1p6a_consurf.spt"</scriptWhenChecked>
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==Disease==
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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Known diseases associated with this structure: Adrenocortical tumor, somatic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=188830 188830]], Carney complex, type 1 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=188830 188830]], Myxoma, intracardiac OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=188830 188830]], Pigmented adrenocortical disease, primary, 1 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=188830 188830]], Spastic paraplegia-7 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602783 602783]], Thyroid carcinoma, papillary OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=188830 188830]]
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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==About this Structure==
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</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=1p6a ConSurf].
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1P6A is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Human_adenovirus_37 Human adenovirus 37]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1P6A OCA].
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<div style="clear:both"></div>
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__TOC__
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==Reference==
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</StructureSection>
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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:[http://www.ncbi.nlm.nih.gov/pubmed/12716886 12716886]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Human adenovirus 37]]
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[[Category: Human adenovirus 12]]
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[[Category: Protein complex]]
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[[Category: Large Structures]]
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[[Category: Bewley, M C.]]
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[[Category: Bewley MC]]
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[[Category: Flanagan, J M.]]
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[[Category: Flanagan JM]]
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[[Category: Freimuth, P.]]
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[[Category: Freimuth P]]
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[[Category: Graziano, V.]]
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[[Category: Graziano V]]
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[[Category: Howitt, J.]]
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[[Category: Howitt J]]
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[[Category: viral protein]]
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[[Category: virus]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:20:24 2008''
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Current revision

STRUCTURAL BASIS FOR VARIATION IN ADENOVIRUS AFFINITY FOR THE CELLULAR RECEPTOR CAR (S489Y MUTANT)

PDB ID 1p6a

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