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TitleComplex structure of the fission yeast SREBP-SCAP binding domains reveals an oligomeric organization.
Journal, issue, pagesCell Res, Vol. 26, Issue 11, Page 1197-1211, Year 2016
Publish dateNov 4, 2016
AuthorsXin Gong / Hongwu Qian / Wei Shao / Jingxian Li / Jianping Wu / Jun-Jie Liu / Wenqi Li / Hong-Wei Wang / Peter Espenshade / Nieng Yan /
PubMed AbstractSterol 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. ...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.
External linksCell Res / PubMed:27811944 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution3.501 - 5.4 Å
Structure data

9537

5grs

EMDB-9537, PDB-5grs:
Complex structure of the fission yeast SREBP-SCAP binding domains
Method: EM (single particle) / Resolution: 5.4 Å

PDB-5gpd:
Crystal structure of the binding domain of SREBP from fission yeast
Method: X-RAY DIFFRACTION / Resolution: 3.501 Å

Source
  • Schizosaccharomyces pombe 972h- (yeast)
  • schizosaccharomyces pombe (strain 972 / atcc 24843) (yeast)
KeywordsDNA BINDING PROTEIN / Regulation domain / PROTEIN TRANSPORT / protein complex

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