The structure of the human centrin 2-xeroderma pigmentosum group C protein complex

J Biol Chem. 2006 Jul 7;281(27):18746-52. doi: 10.1074/jbc.M513667200. Epub 2006 Apr 20.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Binding Sites
  • Calcium
  • Calcium-Binding Proteins / chemistry*
  • Calcium-Binding Proteins / metabolism
  • Cell Cycle Proteins / chemistry*
  • Cell Cycle Proteins / metabolism
  • DNA Repair
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / metabolism
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Protein Binding
  • Protein Structure, Tertiary
  • Xeroderma Pigmentosum / metabolism


  • CETN2 protein, human
  • Calcium-Binding Proteins
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Peptide Fragments
  • XPC protein, human
  • Calcium

Associated data

  • PDB/2GGM