Structural advances in sterol-sensing domain-containing proteins

Xuelan Wu, Renhong Yan, Pingping Cao, Hongwu Qian, Nieng Yan

Research output: Contribution to journalReview articlepeer-review

11 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)289-300
Number of pages12
JournalTrends in Biochemical Sciences
Issue number4
StatePublished - Apr 2022

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology


  • Insig
  • Niemann-Pick disease type C1 (NPC1)
  • Patched
  • Scap
  • cholesterol metabolism
  • cryo-EM


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