Article abstract
Nature Structural & Molecular Biology 15, 980 - 984 (2008)
Published online: 17 August 2008 | doi:10.1038/nsmb.1478
Structural basis for group A trichothiodystrophy
Denis E Kainov1,2, Marc Vitorino1, Jean Cavarelli1, Arnaud Poterszman1 & Jean-Marc Egly1
Abstract
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 
-strand addition and coiled coils interactions between terminal 
-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.
- Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, BP 163, 67404 Illkirch Cedex, France.
- Present address: Laboratoire National de Santé, 20A rue Auguste Lumière, L-1011 Luxembourg.
Correspondence to: Arnaud Poterszman1 e-mail: Arnaud.Poterszman@igbmc.u-strasbg.fr
Correspondence to: Jean-Marc Egly1 e-mail: Jean-Marc.Egly@igbmc.u-strasbg.fr
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