Crystal structure of the Rad3/XPD regulatory domain of Ssl1/p44.
Fiche publication
Date publication
mars 2015
Auteurs
Membres identifiés du Cancéropôle Est :
Dr EGLY Jean-Marc
Tous les auteurs :
Kim JS, Saint-Andre C, Lim HS, Hwang CS, Egly JM, Cho Y
Lien Pubmed
Résumé
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 beta-sheet is sandwiched between three alpha helices on both sides. Structural and biochemical analyses of Ssl1/p44 revealed that the beta4-alpha5 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 beta4-alpha5 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.
Référence
J Biol Chem. 2015 Mar 27;290(13):8321-30