2RVB

Solution structure of the complex between XPC acidic domain and TFIIH p62 PH domain

Summary for 2RVB

• Entry DOI: 10.2210/pdb2rvb/pdb
• NMR Information: BMRB: 11594
• Descriptor: DNA repair protein complementing XP-C cells, General transcription factor IIH subunit 1 (2 entities in total)
• Functional Keywords: dna repair, human xpc, acidic domain, general transcription factor, human tfiih p62, ph domain, dna binding protein-transcription complex, dna binding protein/transcription
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: Q01831 P32780
• Total number of polymer chains: 2
• Total formula weight: 18375.61

Authors

Okuda, M.,Nishimura, Y. (deposition date: 2015-07-01, release date: 2015-09-09, Last modification date: 2024-05-01)

Primary citation

Okuda, M.,Kinoshita, M.,Kakumu, E.,Sugasawa, K.,Nishimura, Y.
Structural Insight into the Mechanism of TFIIH Recognition by the Acidic String of the Nucleotide Excision Repair Factor XPC.
Structure, 23:1827-1837, 2015

PubMed Abstract: In global genome repair (GGR), XPC detects damaged nucleotides and recruits TFIIH complex. The small acidic region of XPC binds to the pleckstrin homology (PH) domain of TFIIH subunit p62; however, the recognition mechanism remains elusive. Here, we use nuclear magnetic resonance to present the tertiary structure of XPC bound to the PH domain. The XPC acidic region forms a long string stabilized by insertion of Trp133 and Val136 into two separate hollows of the PH domain, coupled with extensive electrostatic contacts. Analysis of several XPC mutants revealed that particularly Trp133 is essential for binding to the PH domain. In cell lines stably expressing mutant XPC, alanine substitution at Trp133 or Trp133/Val136 compromised UV resistance, recruitment of TFIIH to DNA damage, and removal of UV-induced photoproducts from genomic DNA. These findings show how TFIIH complex is recruited by XPC to damaged DNA, advancing our understanding of the early stage of GGR.

PubMed: 26278177
DOI: 10.1016/j.str.2015.07.009

Experimental method

SOLUTION NMR