1. Structural basis for group A trichothiodystrophy
- Author
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Jean Cavarelli, Jean-Marc Egly, Denis E. Kainov, Marc Vitorino, Arnaud Poterszman, Peney, Maité, Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I
- Subjects
Models, Molecular ,Saccharomyces cerevisiae Proteins ,DNA Repair ,Transcription, Genetic ,DNA repair ,Protein subunit ,Trichothiodystrophy ,Saccharomyces cerevisiae ,Biology ,Crystallography, X-Ray ,03 medical and health sciences ,0302 clinical medicine ,Structural Biology ,Transcription (biology) ,medicine ,Humans ,Trichothiodystrophy Syndromes ,Protein Interaction Domains and Motifs ,Molecular Biology ,Gene ,030304 developmental biology ,Genetics ,0303 health sciences ,[SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM] ,medicine.disease ,[SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM] ,Yeast ,Recombinant Proteins ,Cell biology ,Multiprotein Complexes ,Mutation ,Transcription factor II H ,Transcription Factor TFIIH ,030217 neurology & neurosurgery ,Intracellular - Abstract
International audience; 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.
- Published
- 2009