Department of Chemistry, Princeton University, Princeton, NJ 08544, USA.
Westlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, 18 Shilongshan Road, Hangzhou 310024, Zhejiang Province, China; Institute of Biology, Westlake Institute for Advanced Study, 18 Shilongshan Road, Hangzhou 310024, Zhejiang Province, China.
Trends Biochem Sci. 2022 Apr;47(4):289-300. doi: 10.1016/j.tibs.2021.12.005. Epub 2022 Jan 7.
The sterol-sensing domain (SSD) is present in several membrane proteins that function in cholesterol metabolism, transport, and signaling. Recent progress in structural studies of SSD-containing proteins, such as sterol regulatory element-binding protein (SREBP)-cleavage activating protein (Scap), Patched, Niemann-Pick disease type C1 (NPC1), and related proteins, reveals a conserved core that is essential for their sterol-dependent functions. This domain, by its name, 'senses' the presence of sterol substrates through interactions and may modulate protein behaviors with changing sterol levels. We summarize recent advances in structural and mechanistic investigations of these proteins and propose to divide them to two classes: M for 'moderator' proteins that regulate sterol metabolism in response to membrane sterol levels, and T for 'transporter' proteins that harbor inner tunnels for cargo trafficking across cellular membranes.
固醇感应结构域（SSD）存在于几种参与胆固醇代谢、运输和信号转导的膜蛋白中。近年来，对包含 SSD 的蛋白质（如固醇调节元件结合蛋白（SREBP）-切割激活蛋白（Scap）、 patched、尼曼-匹克病 C1 型（NPC1）和相关蛋白）的结构研究取得了进展，揭示了其固醇依赖性功能所必需的保守核心。该结构域通过与固醇底物的相互作用，如其名称所示，“感知”固醇底物的存在，并可能随着固醇水平的变化调节蛋白质的行为。我们总结了这些蛋白质的结构和机制研究的最新进展，并提出将它们分为两类：M 类为“调节剂”蛋白，它们根据膜固醇水平调节固醇代谢，T 类为“转运体”蛋白，它们具有用于货物跨细胞膜运输的内部隧道。
