2OBH

Centrin-XPC peptide

Summary for 2OBH

• Entry DOI: 10.2210/pdb2obh/pdb
• Related: 2A4J 2GGM
• Descriptor: Centrin-2, DNA-repair protein complementing XP-C cells, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: dna repair complex ef hand superfamily protein-peptide complex, cell cycle
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm, cytoskeleton, centrosome, centriole: P41208; Nucleus: Q01831
• Total number of polymer chains: 4
• Total formula weight: 37422.94

Authors

Charbonnier, J.B. (deposition date: 2006-12-19, release date: 2007-10-09, Last modification date: 2024-11-06)

Primary citation

Charbonnier, J.B.,Renaud, E.,Miron, S.,Le Du, M.H.,Blouquit, Y.,Duchambon, P.,Christova, P.,Shosheva, A.,Rose, T.,Angulo, J.F.,Craescu, C.T.
Structural, thermodynamic, and cellular characterization of human centrin 2 interaction with xeroderma pigmentosum group C protein.
J.Mol.Biol., 373:1032-1046, 2007

PubMed Abstract: 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.

PubMed: 17897675
DOI: 10.1016/j.jmb.2007.08.046

Experimental method

X-RAY DIFFRACTION (1.8 Å)