Fiche publication
Date publication
septembre 2008
Auteurs
Membres identifiés du Cancéropôle Est :
Pr CAVARELLI Jean
,
Dr EGLY Jean-Marc
,
Dr POTERSZMAN Arnaud
Tous les auteurs :
Kainov DE, Vitorino M, Cavarelli J, Poterszman A, Egly JM
Lien Pubmed
Résumé
Patients with the rare neurodevelopmental repair syndrome known as group A trichothiodystrophy (TTD-A) carry mutations in the gene encoding the p8 subunit of the transcription and DNA repair factor TFIIH. Here we describe the crystal structure of a minimal complex between Tfb5, the yeast ortholog of p8, and the C-terminal domain of Tfb2, the yeast p52 subunit of TFIIH. The structure revealed that these two polypeptides adopt the same fold, forming a compact pseudosymmetric heterodimer via a beta-strand addition and coiled coils interactions between terminal alpha-helices. Furthermore, Tfb5 protects a hydrophobic surface in Tfb2 from solvent, providing a rationale for the influence of p8 in the stabilization of p52 and explaining why mutations that weaken p8-p52 interactions lead to a reduced intracellular TFIIH concentration and a defect in nucleotide-excision repair, a common feature of TTD cells.
Référence
Nat Struct Mol Biol. 2008 Sep;15(9):980-4.
