Structural advances in sterol-sensing domain-containing proteins. Issue 4 (April 2022)

• Record Type: Journal Article
• Authors: Wu, Xuelan; Yan, Renhong; Cao, Pingping; Qian, Hongwu; Yan, Nieng
• Is Part Of: Trends in biochemical sciences. Volume 47:Issue 4(2022)
• Page Start: 289
• Page End: 300
• Publication Date: 2022-04
• Subjects: cholesterol metabolism -- Scap -- Insig -- Niemann-Pick disease type C1 (NPC1) -- Patched -- cryo-EM; Biochemistry -- Periodicals; 572
• DOI: 10.1016/j.tibs.2021.12.005
• Languages: English
• ISSNs: 0968-0004

Abstract

Abstract : 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. Highlights: Sterol-sensing domain (SSD)-containing proteins play a key role in sterol sensing, transport, and signaling. Structural comparison redefines the elements that constitute the SSD. Conformational changes of SSD are crucial for sterol sensing and transport. Structures of SSD-containing transporters reveal the transport path of sterols.