ArticleThe Journal of biological chemistry2016
Direct Demonstration That Loop1 of Scap Binds to Loop7: A CRUCIAL EVENT IN CHOLESTEROL HOMEOSTASIS.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Competition between a transmembrane helix on Scap and a membrane cholesterol regulates Scap-Insig interaction and SREBP activation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- PI3K Signaling at the Crossroads of Lipid Metabolism and Cancer.Advances in experimental medicine and biology · 2025Review
- DGAT2 inhibition blocks SREBP-1 cleavage and improves hepatic steatosis by increasing phosphatidylethanolamine in the ER.Cell metabolism · 2024Article
- A cholesterol-binding bacterial toxin provides a strategy for identifying a specific Scap inhibitor that blocks lipid synthesis in animal cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The role of cholesterol binding in the control of cholesterol by the Scap-Insig system.European biophysics journal : EBJ · 2022Article
- Scap structures highlight key role for rotation of intertwined luminal loops in cholesterol sensing.Cell · 2021Article
- Ring finger protein 5 activates sterol regulatory element-binding protein 2 (SREBP2) to promote cholesterol biosynthesis via inducing polyubiquitination of SREBP chaperone SCAP.The Journal of biological chemistry · 2020Article
- Retrospective on Cholesterol Homeostasis: The Central Role of Scap.Annual review of biochemistry · 2018Review
- SREBPs in Lipid Metabolism, Insulin Signaling, and Beyond.Trends in biochemical sciences · 2018Review
- SREBP-regulated lipid metabolism: convergent physiology - divergent pathophysiology.Nature reviews. Endocrinology · 2017Review
- Cholesterol-induced conformational changes in the sterol-sensing domain of the Scap protein suggest feedback mechanism to control cholesterol synthesis.The Journal of biological chemistry · 2017Article
- Heat Shock Protein 90 Modulates Lipid Homeostasis by Regulating the Stability and Function of Sterol Regulatory Element-binding Protein (SREBP) and SREBP Cleavage-activating Protein.The Journal of biological chemistry · 2017Article
- Defective cholesterol metabolism in amyotrophic lateral sclerosis.Journal of lipid research · 2017Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Cholesterol homeostasis is mediated by Scap, a polytopic endoplasmic reticulum (ER) protein that transports sterol regulatory element-binding proteins from the ER to Golgi, where they are processed to forms that activate cholesterol synthesis. Scap has eight transmembrane helices and two large luminal loops, designated Loop1 and Loop7. We earlier provided indirect evidence that Loop1 binds to Loop7, allowing Scap to bind COPII proteins for transport in coated vesicles. When ER cholesterol rises, it binds to Loop1. We hypothesized that this causes dissociation from Loop7, abrogating COPII binding. Here we demonstrate direct binding of the two loops when expressed as isolated fragments or as a fusion protein. Expressed alone, Loop1 remained intracellular and membrane-bound. When Loop7 was co-expressed, it bound to Loop1, and the soluble complex was secreted. A Loop1-Loop7 fusion protein was also secreted, and the two loops remained bound when the linker between them was cleaved by a protease. Point mutations that disrupt the Loop1-Loop7 interaction prevented secretion of the Loop1-Loop7 fusion protein. These data provide direct documentation of intramolecular Loop1-Loop7 binding, a central event in cholesterol homeostasis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.