普林斯顿大学颜宁、清华大学闫创业等研究人员合作揭示了Insig-2与Scap的相互作用如何受固醇调节。相关论文于2021年1月14日在线发表在《科学》杂志上。

研究人员报道了在25-羟基胆固醇（25HC）存在下人源Scap和Insig-2复合物的冷冻电镜结构，并以平均3.7Å的分辨率确定了跨膜（TM）结构域。研究人员解析了Scap中的固醇感知结构域（SSD）和Insig-2中的全部六个TM。25HC分子夹在Scap的S4-S6片段与膜腔小叶中Insig-2的TM 3/4之间。Scap-S4段中间的展开对于25HC和Insig的结合至关重要。

据了解，SREBP途径控制固醇的细胞稳态。Scap和Insig-1/2是这一途径的关键参与者，它们是嵌入膜中的固醇传感器。Scap和Insigs的25HC依赖性结合充当SREBP途径的核心开关。

附：英文原文

Title: A structure of human Scap bound to Insig-2 suggests how their interaction is regulated by sterols

Author: Renhong Yan, Pingping Cao, Wenqi Song, Hongwu Qian, Ximing Du, Hudson W. Coates, Xin Zhao, Yaning Li, Shuai Gao, Xin Gong, Ximing Liu, Jianhua Sui, Jianlin Lei, Hongyuan Yang, Andrew J. Brown, Qiang Zhou, Chuangye Yan, Nieng Yan

Issue&Volume: 2021/01/14

Abstract: The SREBP pathway controls cellular homeostasis of sterols. The key players in this pathway, Scap and Insig-1/2, are membrane-embedded sterol sensors. 25-hydroxycholesterol (25HC)-dependent association of Scap and Insigs acts as the master switch for the SREBP pathway. Here, we present cryo-EM 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 . The sterol sensing domain (SSD) in Scap and all six TMs in Insig-2 were resolved. A 25HC molecule is sandwiched between the S4-S6 segments in Scap and TMs 3/4 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.

DOI: 10.1126/science.abb2224

Source: https://science.sciencemag.org/content/early/2021/01/13/science.abb2224