Structural advances in sterol-sensing domain-containing proteins.

TitleStructural advances in sterol-sensing domain-containing proteins.
Publication TypeJournal Article
Year of Publication2022
AuthorsWu, X, Yan, R, Cao, P, Qian, H, Yan, N
JournalTrends Biochem Sci
Volume47
Issue4
Pagination289-300
Date Published2022 04
ISSN0968-0004
KeywordsCarrier Proteins, Intracellular Signaling Peptides and Proteins, Membrane Proteins, Niemann-Pick C1 Protein, Sterols
Abstract

<p>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.</p>

DOI10.1016/j.tibs.2021.12.005
Alternate JournalTrends Biochem Sci
PubMed ID35012873