Details

Autor(en) / Beteiligte

• Gong, Xin
• Li, Jingxian
• Shao, Wei
• Wu, Jianping
• Qian, Hongwu
• Ren, Ruobing
• Espenshade, Peter
• Yan, Nieng

Titel

Structure of the WD40 domain of SCAP from fission yeast reveals the molecular basis for SREBP recognition

Ist Teil von

• Cell research, 2015-04, Vol.25 (4), p.401-411

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• The sterol regulatory element-binding protein （SREBP） and SREBP cleavage-activating protein （SCAP） are central players in the SREBP pathway, which control the cellular lipid homeostasis. SCAP binds to SREBP through their carboxyl （C） domains and escorts SREBP from the endoplasmic reticulum to the Golgi upon sterol depletion. A conserved pathway, with the homologues of SREBP and SCAP being Srel and Scpl, was identified in fission yeast Schizosaccharomycespombe. Here we report the in vitro reconstitution of the complex between the C domains of Srel and Scpl as well as the crystal structure of the WD40 domain of Scpl at 2.1 ~ resolution. The structure reveals an eight-bladed [5-propeller that exhibits several distinctive features from a canonical WD40 repeat domain. Structural and biochemical characterization led to the identification of two Scpl elements that are involved in Srel recognition, an Arg/Lys-enriched surface patch on the top face of the WD40 propeller and a 30-residue C-terminal tail. The struc- tural and biochemical findings were corroborated by in vivo examinations. These studies serve as a framework for the mechanistic understanding and further functional characterization of the SREBP and SCAP proteins in fission yeast and higher organisms.