Structural basis for group A trichothiodystrophy. - Archive ouverte HAL Access content directly
Journal Articles Nature Structural and Molecular Biology Year : 2008

Structural basis for group A trichothiodystrophy.

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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 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.
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Dates and versions

inserm-00357162 , version 1 (29-01-2009)

Identifiers

  • HAL Id : inserm-00357162 , version 1
  • PUBMED : 19172752

Cite

Denis E. Kainov, Marc Vitorino, Jean Cavarelli, Arnaud Poterszman, Jean-Marc Egly. Structural basis for group A trichothiodystrophy.. Nature Structural and Molecular Biology, 2008, 15 (9), pp.980-4. ⟨inserm-00357162⟩
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