5GRS

Complex structure of the fission yeast SREBP-SCAP binding domains

Summary for 5GRS

• Entry DOI: 10.2210/pdb5grs/pdb
• Related: 4YHC 5GPD
• EMDB information: 9537
• Descriptor: Sterol regulatory element-binding protein cleavage-activating protein, Sterol regulatory element-binding protein 1 (3 entities in total)
• Functional Keywords: protein complex, protein transport
• Biological source: Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast); More
• Total number of polymer chains: 12
• Total formula weight: 348576.66

Authors

Gong, X.,Qian, H.W.,Wu, J.P.,Yan, N. (deposition date: 2016-08-12, release date: 2016-12-14, Last modification date: 2024-10-30)

Primary citation

Gong, X.,Qian, H.W.,Shao, W.,Li, J.,Wu, J.P.,Liu, J.J.,Li, W.,Wang, H.W.,Espenshade, P.,Yan, N.
Complex structure of the fission yeast SREBP-SCAP binding domains reveals an oligomeric organization
Cell Res., 26:1197-1211, 2016

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

PubMed: 27811944
DOI: 10.1038/cr.2016.123

Experimental method

ELECTRON MICROSCOPY (5.4 Å)