title: Solution structure of the C-terminal domain of TFIIH P44 subunit reveals a novel type of C4C4 ring domain involved in protein-protein interactions.
abstract: The human general transcription factor TFIIH is involved in both transcription and DNA nucleotide excision repair. Among the 10 subunits of the complex, p44 subunit plays a crucial role in both mechanisms. Its N-terminal domain interacts with the XPD helicase, whereas its C-terminal domain is involved specifically in the promoter escape activity. By mutating an exposed and non-conserved cysteine residue into a serine, we produced a soluble mutant of p44-(321-395) suitable for solution structure determination. The domain adopts a C4C4 RING domain structure with sequential organization of beta-strands that is related to canonical RING domains by a circular permutation of the beta-sheet elements. Analysis of the molecular surface and mutagenesis experiments suggests that the binding of p44-(321-395) to TFIIH p34 subunit is not mediated by electrostatic interactions and, thus, differs from previously reported interaction mechanisms involving RING domains.
authors.affiliation: Département de Biologie et de Génomique Structurales, Institut de Génétique et de Biologie Moléculaire et Cellulaire UMR 7104, 1, rue Laurent Fries, BP 10142, 67404 Illkirch cedex, France.
authors.forename: Esther
authors.initials: E
authors.lastname: Kellenberger
authors.forename: Cyril
authors.initials: C
authors.lastname: Dominguez
authors.forename: Sébastien
authors.initials: S
authors.lastname: Fribourg
authors.forename: Emeric
authors.initials: E
authors.lastname: Wasielewski
authors.forename: Dino
authors.initials: D
authors.lastname: Moras
authors.forename: Arnaud
authors.initials: A
authors.lastname: Poterszman
authors.forename: Rolf
authors.initials: R
authors.lastname: Boelens
authors.forename: Bruno
authors.initials: B
authors.lastname: Kieffer
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D003545:Cysteine / Q000737:chemistry; D018076:DNA, Complementary / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D016297:Mutagenesis, Site-Directed; D017510:Protein Folding; D017433:Protein Structure, Secondary; D021122:Protein Subunits / Q000737:chemistry* / Q000235:genetics; D011994:Recombinant Proteins; D016415:Sequence Alignment; D012996:Solutions; D051758:Transcription Factor TFIIH; D019473:Transcription Factors, TFII / Q000737:chemistry* / Q000235:genetics; D014162:Transfection; D015032:Zinc / Q000737:chemistry
chemical_list: D018076:DNA, Complementary; D021122:Protein Subunits; D011994:Recombinant Proteins; D012996:Solutions; D019473:Transcription Factors, TFII; D051758:Transcription Factor TFIIH; D015032:Zinc; D003545:Cysteine