| Literature DB >> 33446483 |
Renhong Yan1,2, Pingping Cao3, Wenqi Song3, Hongwu Qian4, Ximing Du5, Hudson W Coates5, Xin Zhao3, Yaning Li3, Shuai Gao4, Xin Gong6, Ximing Liu7, Jianhua Sui7,8, Jianlin Lei9, Hongyuan Yang5, Andrew J Brown5, Qiang Zhou1,2, Chuangye Yan10, Nieng Yan11.
Abstract
The sterol regulatory element-binding protein (SREBP) pathway controls cellular homeostasis of sterols. The key players in this pathway, Scap and Insig-1 and -2, are membrane-embedded sterol sensors. The 25-hydroxycholesterol (25HC)-dependent association of Scap and Insig acts as the master switch for the SREBP pathway. Here, we present cryo-electron microscopy analysis of the human Scap and Insig-2 complex in the presence of 25HC, with the transmembrane (TM) domains determined at an average resolution of 3.7 angstrom. The sterol-sensing domain in Scap and all six TMs in Insig-2 were resolved. A 25HC molecule is sandwiched between the S4 to S6 segments in Scap and TMs 3 and 4 in Insig-2 in the luminal leaflet of the membrane. Unwinding of the middle of the Scap-S4 segment is crucial for 25HC binding and Insig association.Entities:
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Year: 2021 PMID： 33446483 DOI： 10.1126/science.abb2224
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728