2obh

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{{STRUCTURE_2obh| PDB=2obh | SCENE= }}
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==Centrin-XPC peptide==
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===Centrin-XPC peptide===
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<StructureSection load='2obh' size='340' side='right' caption='[[2obh]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
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{{ABSTRACT_PUBMED_17897675}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2obh]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OBH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2OBH FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene><br>
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<tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene></td></tr>
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<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2ggm|2ggm]], [[2a4j|2a4j]]</td></tr>
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<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CETN2, CALT, CEN2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<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=2obh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2obh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2obh RCSB], [http://www.ebi.ac.uk/pdbsum/2obh PDBsum]</span></td></tr>
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<table>
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== Disease ==
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[[http://www.uniprot.org/uniprot/XPC_HUMAN XPC_HUMAN]] Defects in XPC are a cause of xeroderma pigmentosum complementation group C (XP-C) [MIM:[http://omim.org/entry/278720 278720]]; also known as xeroderma pigmentosum III (XP3). XP-C is a rare human autosomal recessive disease characterized by solar sensitivity, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities.<ref>PMID:19609301</ref> <ref>PMID:17682058</ref> <ref>PMID:17355181</ref> <ref>PMID:8298653</ref> <ref>PMID:10766188</ref>
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== Function ==
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[[http://www.uniprot.org/uniprot/CETN2_HUMAN CETN2_HUMAN]] Plays a fundamental role in microtubule-organizing center structure and function. Required for centriole duplication and correct spindle formation. Has a role in regulating cytokinesis and genome stability via cooperation with CALM1 and CEP110.<ref>PMID:8248209</ref> <ref>PMID:11279143</ref> <ref>PMID:12176356</ref> <ref>PMID:15964821</ref> <ref>PMID:17154534</ref> <ref>PMID:16760425</ref> Involved in global genome nucleotide excision repair (GG-NER) by acting as component of the XPC complex. Cooperatively with RAD23B appears to stabilize XPC. In vitro, stimulates DNA binding of the XPC:RAD23B dimer.<ref>PMID:8248209</ref> <ref>PMID:11279143</ref> <ref>PMID:12176356</ref> <ref>PMID:15964821</ref> <ref>PMID:17154534</ref> <ref>PMID:16760425</ref> The XPC complex is proposed to represent the first factor bound at the sites of DNA damage and together with other core recognition factors, XPA, RPA and the TFIIH complex, is part of the pre-incision (or initial recognition) complex. The XPC complex recognizes a wide spectrum of damaged DNA characterized by distortions of the DNA helix such as single-stranded loops, mismatched bubbles or single stranded overhangs. The orientation of XPC complex binding appears to be crucial for inducing a productive NER. XPC complex is proposed to recognize and to interact with unpaired bases on the undamaged DNA strand which is followed by recruitment of the TFIIH complex and subsequent scanning for lesions in the opposite strand in a 5'-to-3' direction by the NER machinery. Cyclobutane pyrimidine dimers (CPDs) which are formed upon UV-induced DNA damage esacpe detection by the XPC complex due to a low degree of structural perurbation. Instead they are detected by the UV-DDB complex which in turn recruits and cooperates with the XPC complex in the respective DNA repair.<ref>PMID:8248209</ref> <ref>PMID:11279143</ref> <ref>PMID:12176356</ref> <ref>PMID:15964821</ref> <ref>PMID:17154534</ref> <ref>PMID:16760425</ref> [[http://www.uniprot.org/uniprot/XPC_HUMAN XPC_HUMAN]] Involved in global genome nucleotide excision repair (GG-NER) by acting as damage sensing and DNA-binding factor component of the XPC complex. Has only a low DNA repair activity by itself which is stimulated by RAD23B and RAD23A. Has a preference to bind DNA containing a short single-stranded segment but not to damaged oligonucleotides. This feature is proposed to be related to a dynamic sensor function: XPC can rapidly screen duplex DNA for non-hydrogen-bonded bases by forming a transient nucleoprotein intermediate complex which matures into a stable recognition complex through an intrinsic single-stranded DNA-binding activity.<ref>PMID:9734359</ref> <ref>PMID:10734143</ref> <ref>PMID:10873465</ref> <ref>PMID:12509299</ref> <ref>PMID:12547395</ref> <ref>PMID:19609301</ref> <ref>PMID:19941824</ref> <ref>PMID:20649465</ref> <ref>PMID:20028083</ref> <ref>PMID:20798892</ref> The XPC complex is proposed to represent the first factor bound at the sites of DNA damage and together with other core recognition factors, XPA, RPA and the TFIIH complex, is part of the pre-incision (or initial recognition) complex. The XPC complex recognizes a wide spectrum of damaged DNA characterized by distortions of the DNA helix such as single-stranded loops, mismatched bubbles or single stranded overhangs. The orientation of XPC complex binding appears to be crucial for inducing a productive NER. XPC complex is proposed to recognize and to interact with unpaired bases on the undamaged DNA strand which is followed by recruitment of the TFIIH complex and subsequent scanning for lesions in the opposite strand in a 5'-to-3' direction by the NER machinery. Cyclobutane pyrimidine dimers (CPDs) which are formed upon UV-induced DNA damage esacpe detection by the XPC complex due to a low degree of structural perurbation. Instead they are detected by the UV-DDB complex which in turn recruits and cooperates with the XPC complex in the respective DNA repair. In vitro, the XPC:RAD23B dimer is sufficient to initiate NER; it preferentially binds to cisplatin and UV-damaged double-stranded DNA and also binds to a variety of chemically and structurally diverse DNA adducts. XPC:RAD23B contacts DNA both 5' and 3' of a cisplatin lesion with a preference for the 5' side. XPC:RAD23B induces a bend in DNA upon binding. XPC:RAD23B stimulates the activity of DNA glycosylases TDG and SMUG1.<ref>PMID:9734359</ref> <ref>PMID:10734143</ref> <ref>PMID:10873465</ref> <ref>PMID:12509299</ref> <ref>PMID:12547395</ref> <ref>PMID:19609301</ref> <ref>PMID:19941824</ref> <ref>PMID:20649465</ref> <ref>PMID:20028083</ref> <ref>PMID:20798892</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ob/2obh_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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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/chain_selection.php?pdb_ID=2ata ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Human centrin 2 (HsCen2), an EF-hand calcium binding protein, plays a regulatory role in the DNA damage recognition during the first steps of the nucleotide excision repair. This biological action is mediated by the binding to a short fragment (N847-R863) from the C-terminal region of xeroderma pigmentosum group C (XPC) protein. This work presents a detailed structural and energetic characterization of the HsCen2/XPC interaction. Using a truncated form of HsCen2 we obtained a high resolution (1.8 A) X-ray structure of the complex with the peptide N847-R863 from XPC. Structural and thermodynamic analysis of the interface revealed the existence of both electrostatic and apolar inter-molecular interactions, but the binding energy is mainly determined by the burial of apolar bulky side-chains into the hydrophobic pocket of the HsCen2 C-terminal domain. Binding studies with various peptide variants showed that XPC residues W848 and L851 constitute the critical anchoring side-chains. This enabled us to define a minimal centrin binding peptide variant of five residues, which accounts for about 75% of the total free energy of interaction between the two proteins. Immunofluorescence imaging in HeLa cells demonstrated that HsCen2 binding to the integral XPC protein may be observed in living cells, and is determined by the same interface residues identified in the X-ray structure of the complex. Overexpression of XPC perturbs the cellular distribution of HsCen2, by inducing a translocation of centrin molecules from the cytoplasm to the nucleus. The present data confirm that the in vitro structural features of the centrin/XPC peptide complex are highly relevant to the cellular context.
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==Disease==
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Structural, thermodynamic, and cellular characterization of human centrin 2 interaction with xeroderma pigmentosum group C protein.,Charbonnier JB, Renaud E, Miron S, Le Du MH, Blouquit Y, Duchambon P, Christova P, Shosheva A, Rose T, Angulo JF, Craescu CT J Mol Biol. 2007 Nov 2;373(4):1032-46. Epub 2007 Aug 25. PMID:17897675<ref>PMID:17897675</ref>
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[[http://www.uniprot.org/uniprot/XPC_HUMAN XPC_HUMAN]] Defects in XPC are a cause of xeroderma pigmentosum complementation group C (XP-C) [MIM:[http://omim.org/entry/278720 278720]]; also known as xeroderma pigmentosum III (XP3). XP-C is a rare human autosomal recessive disease characterized by solar sensitivity, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities.<ref>PMID:19609301</ref><ref>PMID:17682058</ref><ref>PMID:17355181</ref><ref>PMID:8298653</ref><ref>PMID:10766188</ref>
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==Function==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[http://www.uniprot.org/uniprot/CETN2_HUMAN CETN2_HUMAN]] Plays a fundamental role in microtubule-organizing center structure and function. Required for centriole duplication and correct spindle formation. Has a role in regulating cytokinesis and genome stability via cooperation with CALM1 and CEP110.<ref>PMID:8248209</ref><ref>PMID:11279143</ref><ref>PMID:12176356</ref><ref>PMID:15964821</ref><ref>PMID:17154534</ref><ref>PMID:16760425</ref> Involved in global genome nucleotide excision repair (GG-NER) by acting as component of the XPC complex. Cooperatively with RAD23B appears to stabilize XPC. In vitro, stimulates DNA binding of the XPC:RAD23B dimer.<ref>PMID:8248209</ref><ref>PMID:11279143</ref><ref>PMID:12176356</ref><ref>PMID:15964821</ref><ref>PMID:17154534</ref><ref>PMID:16760425</ref> The XPC complex is proposed to represent the first factor bound at the sites of DNA damage and together with other core recognition factors, XPA, RPA and the TFIIH complex, is part of the pre-incision (or initial recognition) complex. The XPC complex recognizes a wide spectrum of damaged DNA characterized by distortions of the DNA helix such as single-stranded loops, mismatched bubbles or single stranded overhangs. The orientation of XPC complex binding appears to be crucial for inducing a productive NER. XPC complex is proposed to recognize and to interact with unpaired bases on the undamaged DNA strand which is followed by recruitment of the TFIIH complex and subsequent scanning for lesions in the opposite strand in a 5'-to-3' direction by the NER machinery. Cyclobutane pyrimidine dimers (CPDs) which are formed upon UV-induced DNA damage esacpe detection by the XPC complex due to a low degree of structural perurbation. Instead they are detected by the UV-DDB complex which in turn recruits and cooperates with the XPC complex in the respective DNA repair.<ref>PMID:8248209</ref><ref>PMID:11279143</ref><ref>PMID:12176356</ref><ref>PMID:15964821</ref><ref>PMID:17154534</ref><ref>PMID:16760425</ref> [[http://www.uniprot.org/uniprot/XPC_HUMAN XPC_HUMAN]] Involved in global genome nucleotide excision repair (GG-NER) by acting as damage sensing and DNA-binding factor component of the XPC complex. Has only a low DNA repair activity by itself which is stimulated by RAD23B and RAD23A. Has a preference to bind DNA containing a short single-stranded segment but not to damaged oligonucleotides. This feature is proposed to be related to a dynamic sensor function: XPC can rapidly screen duplex DNA for non-hydrogen-bonded bases by forming a transient nucleoprotein intermediate complex which matures into a stable recognition complex through an intrinsic single-stranded DNA-binding activity.<ref>PMID:9734359</ref><ref>PMID:10734143</ref><ref>PMID:10873465</ref><ref>PMID:12509299</ref><ref>PMID:12547395</ref><ref>PMID:19609301</ref><ref>PMID:19941824</ref><ref>PMID:20649465</ref><ref>PMID:20028083</ref><ref>PMID:20798892</ref> The XPC complex is proposed to represent the first factor bound at the sites of DNA damage and together with other core recognition factors, XPA, RPA and the TFIIH complex, is part of the pre-incision (or initial recognition) complex. The XPC complex recognizes a wide spectrum of damaged DNA characterized by distortions of the DNA helix such as single-stranded loops, mismatched bubbles or single stranded overhangs. The orientation of XPC complex binding appears to be crucial for inducing a productive NER. XPC complex is proposed to recognize and to interact with unpaired bases on the undamaged DNA strand which is followed by recruitment of the TFIIH complex and subsequent scanning for lesions in the opposite strand in a 5'-to-3' direction by the NER machinery. Cyclobutane pyrimidine dimers (CPDs) which are formed upon UV-induced DNA damage esacpe detection by the XPC complex due to a low degree of structural perurbation. Instead they are detected by the UV-DDB complex which in turn recruits and cooperates with the XPC complex in the respective DNA repair. In vitro, the XPC:RAD23B dimer is sufficient to initiate NER; it preferentially binds to cisplatin and UV-damaged double-stranded DNA and also binds to a variety of chemically and structurally diverse DNA adducts. XPC:RAD23B contacts DNA both 5' and 3' of a cisplatin lesion with a preference for the 5' side. XPC:RAD23B induces a bend in DNA upon binding. XPC:RAD23B stimulates the activity of DNA glycosylases TDG and SMUG1.<ref>PMID:9734359</ref><ref>PMID:10734143</ref><ref>PMID:10873465</ref><ref>PMID:12509299</ref><ref>PMID:12547395</ref><ref>PMID:19609301</ref><ref>PMID:19941824</ref><ref>PMID:20649465</ref><ref>PMID:20028083</ref><ref>PMID:20798892</ref>
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</div>
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== References ==
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==About this Structure==
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<references/>
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[[2obh]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OBH OCA].
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__TOC__
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</StructureSection>
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==Reference==
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<ref group="xtra">PMID:017897675</ref><ref group="xtra">PMID:016820684</ref><ref group="xtra">PMID:016627479</ref><references group="xtra"/><references/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Charbonnier, J B.]]
[[Category: Charbonnier, J B.]]
[[Category: Cell cycle]]
[[Category: Cell cycle]]
[[Category: Dna repair complex ef hand superfamily protein-peptide complex]]
[[Category: Dna repair complex ef hand superfamily protein-peptide complex]]

Revision as of 19:45, 30 September 2014

Centrin-XPC peptide

2obh, resolution 1.80Å

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