The Structure of the Human Centrin 2-Xeroderma Pigmentosum Group C Protein Complex

Journal Article · Sun Jan 01 04:00:00 EST 2006 · J. Biol. Chem.

DOI:https://doi.org/10.1074/jbc.M513667200· OSTI ID:914141

Thompson, J; Ryan, Z; Salisbury, J; Kumar, R

Human centrin-2 plays a key role in centrosome function and stimulates nucleotide excision repair by binding to the xeroderma pigmentosum group C protein. To determine the structure of human centrin-2 and to develop an understanding of molecular interactions between centrin and xeroderma pigmentosum group C protein, we characterized the crystal structure of calcium-loaded full-length centrin-2 complexed with a xeroderma pigmentosum group C peptide. Our structure shows that the carboxyl-terminal domain of centrin-2 binds this peptide and two calcium atoms, whereas the amino-terminal lobe is in a closed conformation positioned distantly by an ordered {alpha}-helical linker. A stretch of the amino-terminal domain unique to centrins appears disordered. Two xeroderma pigmentosum group C peptides both bound to centrin-2 also interact to form an {alpha}-helical coiled-coil. The interface between centrin-2 and each peptide is predominantly nonpolar, and key hydrophobic residues of XPC have been identified that lead us to propose a novel binding motif for centrin.

• Research Organization: Brookhaven National Laboratory (BNL) National Synchrotron Light Source
• Sponsoring Organization: Doe - Office Of Science
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 914141
• Report Number(s): BNL--78709-2007-JA
• Journal Information: J. Biol. Chem., Journal Name: J. Biol. Chem. Vol. 281; ISSN JBCHA3; ISSN 0021-9258
• Country of Publication: United States
• Language: English

Related Subjects

36 MATERIALS SCIENCE
43 PARTICLE ACCELERATORS
ATOMS
CALCIUM
CRYSTAL STRUCTURE
EXCISION REPAIR
NSLS
NUCLEOTIDES
PEPTIDES
PROTEINS
RESIDUES
national synchrotron light source