2obh: Difference between revisions

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[[Image:2obh.~~jpg~~|left|200px]]

[[Image:2obh.png|left|200px]]

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~~'''~~Centrin-XPC peptide~~'''~~

===Centrin-XPC peptide===

~~==Overview==~~

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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.

The line below this paragraph, {{ABSTRACT_PUBMED_17897675}}, adds the Publication Abstract to the page

(as it appears on PubMed at http://www.pubmed.gov), where 17897675 is the PubMed ID number.

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==About this Structure==

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==Reference==

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:[http://www.ncbi.nlm.nih.gov/pubmed/17897675 17897675]

Crystallization and preliminary X-ray diffraction data of the complex between human centrin 2 and a peptide from the protein XPC., Charbonnier JB, Christova P, Shosheva A, Stura E, Le Du MH, Blouquit Y, Duchambon P, Miron S, Craescu CT, Acta Crystallogr Sect F Struct Biol Cryst Commun. 2006 Jul 1;62(Pt, 7):649-51. Epub 2006 Jun 10. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16820684 16820684]

The structure of the human centrin 2-xeroderma pigmentosum group C protein complex., Thompson JR, Ryan ZC, Salisbury JL, Kumar R, J Biol Chem. 2006 Jul 7;281(27):18746-52. Epub 2006 Apr 20. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16627479 16627479]

[[Category: Homo sapiens]]

[[Category: Protein complex]]

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[[Category: Cell cycle]]

[[Category: Dna repair complex ef hand superfamily protein-peptide complex]]

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-[[Image:2obh.jpg|left|200px]]
+{{Seed}}
+[[Image:2obh.png|left|200px]]
 <!--
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 {{STRUCTURE_2obh|  PDB=2obh  |  SCENE=  }}
-'''Centrin-XPC peptide'''
+===Centrin-XPC peptide===
-==Overview==
+<!--
-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.
+The line below this paragraph, {{ABSTRACT_PUBMED_17897675}}, adds the Publication Abstract to the page
+(as it appears on PubMed at http://www.pubmed.gov), where 17897675 is the PubMed ID number.
+-->
+{{ABSTRACT_PUBMED_17897675}}
 ==About this Structure==
@@ Line 20: / Line 24: @@
 ==Reference==
 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:[http://www.ncbi.nlm.nih.gov/pubmed/17897675 17897675]
+Crystallization and preliminary X-ray diffraction data of the complex between human centrin 2 and a peptide from the protein XPC., Charbonnier JB, Christova P, Shosheva A, Stura E, Le Du MH, Blouquit Y, Duchambon P, Miron S, Craescu CT, Acta Crystallogr Sect F Struct Biol Cryst Commun. 2006 Jul 1;62(Pt, 7):649-51. Epub 2006 Jun 10. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16820684 16820684]
+The structure of the human centrin 2-xeroderma pigmentosum group C protein complex., Thompson JR, Ryan ZC, Salisbury JL, Kumar R, J Biol Chem. 2006 Jul 7;281(27):18746-52. Epub 2006 Apr 20. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16627479 16627479]
 [[Category: Homo sapiens]]
 [[Category: Protein complex]]
@@ Line 25: / Line 33: @@
 [[Category: Cell cycle]]
 [[Category: Dna repair complex ef hand superfamily protein-peptide complex]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 10:33:28 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 15:50:25 2008''