title: Crystal structure of the Rad3/XPD regulatory domain of Ssl1/p44.
abstract: The Ssl1/p44 subunit is a core component of the yeast/mammalian general transcription factor TFIIH, which is involved in transcription and DNA repair. Ssl1/p44 binds to and stimulates the Rad3/XPD helicase activity of TFIIH. To understand the helicase stimulatory mechanism of Ssl1/p44, we determined the crystal structure of the N-terminal regulatory domain of Ssl1 from Saccharomyces cerevisiae. Ssl1 forms a von Willebrand factor A fold in which a central six-stranded β-sheet is sandwiched between three α helices on both sides. Structural and biochemical analyses of Ssl1/p44 revealed that the β4-α5 loop, which is frequently found at the interface between von Willebrand factor A family proteins and cellular counterparts, is critical for the stimulation of Rad3/XPD. Yeast genetics analyses showed that double mutation of Leu-239 and Ser-240 in the β4-α5 loop of Ssl1 leads to lethality of a yeast strain, demonstrating the importance of the Rad3-Ssl1 interactions to cell viability. Here, we provide a structural model for the Rad3/XPD-Ssl1/p44 complex and insights into how the binding of Ssl1/p44 contributes to the helicase activity of Rad3/XPD and cell viability.
authors: From the Department of Life Science, Pohang University of Science and Technology, Pohang 790-784, South Korea and.
authors: Jin Seok
authors: JS
authors: Kim
authors: the Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/UdS, BP163, 67404 Illkirch Cedex, C.U. Strasbourg, France.
authors: Charlotte
authors: C
authors: Saint-André
authors: From the Department of Life Science, Pohang University of Science and Technology, Pohang 790-784, South Korea and.
authors: Hye Seong
authors: HS
authors: Lim
authors: From the Department of Life Science, Pohang University of Science and Technology, Pohang 790-784, South Korea and.
authors: Cheol-Sang
authors: CS
authors: Hwang
authors: the Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/UdS, BP163, 67404 Illkirch Cedex, C.U. Strasbourg, France jean-marc.egly@igbmc.fr.
authors: Jean Marc
authors: JM
authors: Egly
authors: From the Department of Life Science, Pohang University of Science and Technology, Pohang 790-784, South Korea and yunje@postech.ac.kr.
authors: Yunje
authors: Y
authors: Cho
mesh_terms: D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D004265:DNA Helicases / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D051758:Transcription Factor TFIIH / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: C083908:SSL1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D051758:Transcription Factor TFIIH; C061897:Rad3 protein, S cerevisiae; D004265:DNA Helicases
keywords: Crystal Structure; DNA Repair; Nucleotide Excision Repair; Rad3/XPD Helicase; Regulatory Domain of Ssl1/p44; TFIIH; Transcription; Yeast Genetics