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PDBsum entry 2rvb
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DNA binding protein/transcription
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PDB id
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2rvb
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References listed in PDB file
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Key reference
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Title
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Structural insight into the mechanism of tfiih recognition by the acidic string of the nucleotide excision repair factor xpc.
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Authors
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M.Okuda,
M.Kinoshita,
E.Kakumu,
K.Sugasawa,
Y.Nishimura.
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Ref.
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Structure, 2015,
23,
1827-1837.
[DOI no: ]
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PubMed id
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Abstract
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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.
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