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.

中文翻译：

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A组毛滴虫营养不良的结构基础。

患有罕见的神经发育修复综合症的患者被称为A组毛发硫代营养不良症（TTD-A），其编码基因的p8亚基和DNA修复因子TFIIH携带突变。在这里，我们描述了Tfb5（p8的酵母直系同源物）和Tfb2（TFIIH的酵母p52亚基​​）的C末端结构域之间最小复合物的晶体结构。结构表明，这两个多肽采用相同的折叠方式，通过β链加成和末端α-螺旋之间的螺旋卷曲相互作用形成了紧凑的假对称异二聚体。此外，Tfb5保护Tfb2中的疏水表面不受溶剂的影响，