7LKH

Chicken Scap D435V L1-L7 domain / Fab complex focused map

7LKH の概要

• エントリーDOI: 10.2210/pdb7lkh/pdb
• 関連するPDBエントリー: 7LKF
• EMDBエントリー: 23405 23408
• 分子名称: Sterol regulatory element-binding protein cleavage-activating protein, 4G10 Fab heavy chain, 4G10 Fab kappa chain, ... (4 entities in total)
• 機能のキーワード: cholesterol, lipid binding protein
• 由来する生物種: Gallus gallus (Chicken); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 197399.07

構造登録者

Kober, D.L.,Radhakrishnan, A.,Goldstein, J.L.,Brown, M.S.,Clark, L.D.,Bai, X.-C.,Rosenbaum, D.M. (登録日: 2021-02-02, 公開日: 2021-06-30, 最終更新日: 2025-05-28)

主引用文献

Kober, D.L.,Radhakrishnan, A.,Goldstein, J.L.,Brown, M.S.,Clark, L.D.,Bai, X.C.,Rosenbaum, D.M.
Scap structures highlight key role for rotation of intertwined luminal loops in cholesterol sensing.
Cell, 184:3689-, 2021

PubMed Abstract: The cholesterol-sensing protein Scap induces cholesterol synthesis by transporting membrane-bound transcription factors called sterol regulatory element-binding proteins (SREBPs) from the endoplasmic reticulum (ER) to the Golgi apparatus for proteolytic activation. Transport requires interaction between Scap's two ER luminal loops (L1 and L7), which flank an intramembrane sterol-sensing domain (SSD). Cholesterol inhibits Scap transport by binding to L1, which triggers Scap's binding to Insig, an ER retention protein. Here we used cryoelectron microscopy (cryo-EM) to elucidate two structures of full-length chicken Scap: (1) a wild-type free of Insigs and (2) mutant Scap bound to chicken Insig without cholesterol. Strikingly, L1 and L7 intertwine tightly to form a globular domain that acts as a luminal platform connecting the SSD to the rest of Scap. In the presence of Insig, this platform undergoes a large rotation accompanied by rearrangement of Scap's transmembrane helices. We postulate that this conformational change halts Scap transport of SREBPs and inhibits cholesterol synthesis.

PubMed: 34139175
DOI: 10.1016/j.cell.2021.05.019

実験手法

ELECTRON MICROSCOPY (3.5 Å)