ArticleNature chemical biology2023
A common mechanism of Sec61 translocon inhibition by small molecules.
Article in Nature chemical biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 69 citations in OpenAlex.
- A mycobacterial Sec61 inhibitor disrupts lysosome function by blocking Vacuolar-ATPase biosynthesis.European journal of cell biology · 2026Article
- Topogenic sequence recognition at TIM complexes revealed by a stendomycin-bound structure.Nature chemical biology · 2026Article
- Pairwise transmembrane domain insertion during multipass protein biogenesis.Molecular cell · 2026Article
- α-Synuclein blocks endoplasmic reticulum co-translational protein translocation early in Parkinson's disease.Nature communications · 2026Article
- Identification of a Novel De Novo Heterozygous SEC61A1 Variant in a Patient With Severe Congenital Neutropenia.Molecular genetics & genomic medicine · 2026Article
- Comparative transcriptome analysis reveals stress-response pathways as key drivers of nitrogen use efficiency in tobacco under low-nitrogen conditions.BMC plant biology · 2026Article
- Targeted downmodulation of OXTR and Cx43 in the myometrium by SERTIs as a novel tocolytic strategy.Uterine research · 2026Article
- Buruli ulcer.Nature reviews. Disease primers · 2025Review
- Article
- Single-cell RNA-sequencing reveals adventitial fibroblast alterations during mouse atherosclerosis.Atherosclerosis · 2025Article
- Effect of Ipomoeassin F on the Synthesis of Membrane and Secretory Proteins in Triple-Negative Breast Cancer Cells.ACS omega · 2025Article
- SEC61B regulates calcium flux and platelet hyperreactivity in diabetes.The Journal of clinical investigation · 2025Article
- A light-resuming strategy as a screening method for selecting Sec61 inhibitors down-modulating PD-L1 expression.Nature communications · 2025Article
- Lipid Scrambling Pathways in the Sec61 Translocon Complex.Journal of the American Chemical Society · 2025Article
- Exploring METRNL as a novel biomarker in sepsis: diagnostic potential and secretion mechanism.Journal of intensive care · 2025Article
- Inhibition of TSH Receptor Expression by a Cyclotriazadisulfonamide as a Potential Treatment of Graves Hyperthyroidism.Endocrinology · 2025Article
- ER-mitochondria contacts mediate lipid radical transfer via RMDN3/PTPIP51 phosphorylation to reduce mitochondrial oxidative stress.Nature communications · 2025Article
- Structural Modifications Reveal Dual Functions of the C-4 Carbonyl Group in the Fatty Acid Chain of Ipomoeassin F.Molecules (Basel, Switzerland) · 2025Article
- Toward Understanding the Mechanism of Client-Selective Small Molecule Inhibitors of the Sec61 Translocon.Journal of molecular recognition : JMR · 2025Review
- The dual-function of HSP70 in immune response and tumor immunity: from molecular regulation to therapeutic innovations.Frontiers in immunology · 2025Review
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11 authors at 7 institutions in 3 countries.
Funding
Abstract
The Sec61 complex forms a protein-conducting channel in the endoplasmic reticulum membrane that is required for secretion of soluble proteins and production of many membrane proteins. Several natural and synthetic small molecules specifically inhibit Sec61, generating cellular effects that are useful for therapeutic purposes, but their inhibitory mechanisms remain unclear. Here we present near-atomic-resolution structures of human Sec61 inhibited by a comprehensive panel of structurally distinct small molecules-cotransin, decatransin, apratoxin, ipomoeassin, mycolactone, cyclotriazadisulfonamide and eeyarestatin. All inhibitors bind to a common lipid-exposed pocket formed by the partially open lateral gate and plug domain of Sec61. Mutations conferring resistance to the inhibitors are clustered at this binding pocket. The structures indicate that Sec61 inhibitors stabilize the plug domain in a closed state, thereby preventing the protein-translocation pore from opening. Our study provides the atomic details of Sec61-inhibitor interactions and the structural framework for further pharmacological studies and drug design.
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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.