ArticleNature communications2022
Regulated degradation of HMG CoA reductase requires conformational changes in sterol-sensing domain.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 42 citations in OpenAlex.
- Emerging roles of the metabolic regulator 3-hydroxy-3-methylglutaryl coenzyme-CoA reductase in human cancers: From biology to therapeutics.Genes & diseases · 2026Review
- Emerging perspectives in proteostasis: bridging mechanisms and therapeutics for human diseases.Signal transduction and targeted therapy · 2026Review
- Metabolic Disruption and Steatosis Induced by Drinking Water Disinfection Byproducts in HepG2 and HUH7 Cells.Toxics · 2026Article
- 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
- Biological Effects of Calceolarioside A as a Natural Compound: Anti-Ovarian Cancer, Anti-Tyrosinase, and Anti-HMG-CoA Reductase Potentials with Molecular Docking and Dynamics Simulation Studies.Molecular biotechnology · 2026Article
- UBE2J2 sensitizes the ERAD ubiquitination cascade to changes in membrane lipid saturation.Nature communications · 2025Article
- Biomimetic membrane-coated nanoparticles for targeted synergistic therapy of homocysteine-induced atherosclerosis: Dual modulation of cholesterol efflux and reactive oxygen species scavenging.Materials today. Bio · 2025Article
- Dysregulated Cholesterol Metabolism and Its Impact on the Tumour Immune Response in Colorectal Cancer.Journal of cellular and molecular medicine · 2025Review
- Astrocytic-supplied cholesterol drives synaptic gene expression programs in developing neurons and downstream astrocytic transcriptional programs.bioRxiv : the preprint server for biology · 2025Article
- A pipeline for identification of causal mutations in barley identifies Xantha-j as the chlorophyll synthase gene.Plant physiology · 2024Article
- Article
- An AlphaFold Structure Analysis of COQ2 as Key a Component of the Coenzyme Q Synthesis Complex.Antioxidants (Basel, Switzerland) · 2024Article
- Structural analysis of phosphoribosyltransferase-mediated cell wall precursor synthesis in Mycobacterium tuberculosis.Nature microbiology · 2024Article
- Direct binding to sterols accelerates endoplasmic reticulum-associated degradation of HMG CoA reductase.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Doa10/MARCH6 architecture interconnects E3 ligase activity with lipid-binding transmembrane channel to regulate SQLE.Nature communications · 2024Article
- Virgin Camellia Seed Oil Improves Glycolipid Metabolism in the Kidney of High Fat-Fed Rats through AMPK-SREBP Pathway.Nutrients · 2023Article
- N-Acetylaspartate Drives Oligodendroglial Differentiation via Histone Deacetylase Activation.Cells · 2023Article
- MiR-122-5p regulates the mevalonate pathway by targeting p53 in non-small cell lung cancer.Cell death & disease · 2023Article
- The Nox2-ROS-Nlrp3 Inflammasome Signaling Stimulates in the Hematopoietic Stem/Progenitor Cells Lipogenesis to Facilitate Membrane Lipid Raft Formation.Stem cell reviews and reports · 2023Article
- Synthesis, function, and regulation of sterol and nonsterol isoprenoids.Frontiers in molecular biosciences · 2022Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) is the rate-limiting enzyme in cholesterol synthesis and target of cholesterol-lowering statin drugs. Accumulation of sterols in endoplasmic reticulum (ER) membranes accelerates degradation of HMGCR, slowing the synthesis of cholesterol. Degradation of HMGCR is inhibited by its binding to UBIAD1 (UbiA prenyltransferase domain-containing protein-1). This inhibition contributes to statin-induced accumulation of HMGCR, which limits their cholesterol-lowering effects. Here, we report cryo-electron microscopy structures of the HMGCR-UBIAD1 complex, which is maintained by interactions between transmembrane helix (TM) 7 of HMGCR and TMs 2-4 of UBIAD1. Disrupting this interface by mutagenesis prevents complex formation, enhancing HMGCR degradation. TMs 2-6 of HMGCR contain a 170-amino acid sterol sensing domain (SSD), which exists in two conformations-one of which is essential for degradation. Thus, our data supports a model that rearrangement of the TMs in the SSD permits recruitment of proteins that initate HMGCR degradation, a key reaction in the regulatory system that governs cholesterol synthesis.
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