5GRS

Complex structure of the fission yeast SREBP-SCAP binding domains

5GRS の概要

• エントリーDOI: 10.2210/pdb5grs/pdb
• 関連するPDBエントリー: 4YHC 5GPD
• EMDBエントリー: 9537
• 分子名称: Sterol regulatory element-binding protein cleavage-activating protein, Sterol regulatory element-binding protein 1 (3 entities in total)
• 機能のキーワード: protein complex, protein transport
• 由来する生物種: Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast); 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 348576.66

構造登録者

Gong, X.,Qian, H.W.,Wu, J.P.,Yan, N. (登録日: 2016-08-12, 公開日: 2016-12-14, 最終更新日: 2024-10-30)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (5.4 Å)