Solution structure and backbone dynamics of the XPC-binding domain of the human DNA repair protein hHR23B.
Human cells contain two homologs of the yeast RAD23 protein, hHR23A and hHR23B, which participate in the DNA repair process. hHR23B houses a domain (residues 277-332, called XPCB) that binds specifically and directly to the xeroderma pigmentosum group C protein (XPC) to initiate nucleotide excision repair (NER). This domain shares sequence homology with a heat shock chaperonin-binding motif that is also found in the stress-inducible yeast phosphoprotein STI1. We determined the solution structure of a protein fragment containing amino acids 275-342 of hHR23B (termed XPCB-hHR23B) and compared it with the previously reported solution structures of the corresponding domain of hHR23A. The periodic positioning of proline residues in XPCB-hHR23B produced kinked alpha helices and assisted in the formation of a compact domain. Although the overall structure of the XPCB domain was similar in both XPCB-hHR23B and XPCB-hHR23A, the N-terminal part (residues 275-283) of XPCB-hHR23B was more flexible than the corresponding part of hHR23A. We tried to infer the characteristics of this flexibility through (15)N-relaxation studies. The hydrophobic surface of XPCB-hHR23B, which results from the diverse distribution of N-terminal region, might give rise to the functional pleiotropy observed in vivo for hHR23B, but not for hHR23A.
Kim
Byoungkook
B
Department of Chemistry, and National Creative Research Initiative Center for the Repair System of Damaged DNA, Korea Advanced Institute of Science and Technology, South Korea.
Ryu
Kyoung-Seok
KS
Kim
Hyun-Jin
HJ
Cho
Sung-Jae
SJ
Choi
Byong-Seok
BS
D000595:Amino Acid Sequence; D003001:Cloning, Molecular; D004260:DNA Repair; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D016415:Sequence Alignment
D004268:DNA-Binding Proteins; C513287:RAD23B protein, human; C086985:RAD23A protein, human; C086984:XPC protein, human; D045643:DNA Repair Enzymes