Complex structure of the fission yeast SREBP-SCAP binding domains reveals an oligomeric organization

• DOI: 10.1038/cr.2016.123
• Publication Date: 2016-11-04T08:48:57Z
• Authors: Xin Gong; Hongwu Qian; Wei Shao; Jingxian Li; Jianping Wu; Jun-Jie Liu; Wenqi Li; Hong-Wei Wang; Peter Espenshade; Nieng Yan
• Keywords: CTD; Schizosaccharomyces

Sterol regulatory element-binding protein (SREBP) transcription factors are master regulators of cellular lipid homeostasis in mammals and oxygen-responsive hypoxic adaptation fungi. SREBP C-terminus binds to the WD40 domain cleavage-activating (SCAP), which confers sterol regulation by controlling ER-to-Golgi transport SREBP-SCAP complex access activating proteases Golgi. Here, we biochemically structurally show that carboxyl terminal domains (CTD) Sre1 Scp1, fission yeast SCAP, form a functional 4:4 oligomer Sre1-CTD forms dimer dimers. The crystal structure at 3.5 Å cryo-EM 5.4 together with vitro biochemical evidence elucidate three distinct regions required for Scp1 binding, dimerization tetrameric formation. Finally, these identified validated context, demonstrating proper oligomeric formation is activation.