ArticleMolecular cell2020
Structure of the Inhibited State of the Sec Translocon.
Article in Molecular cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
37 citing papers in PubMed, 71 citations in OpenAlex.
- Aberrant stromal tissue factor localisation and mycolactone-driven vascular dysfunction, exacerbated by IL-1β, are linked to fibrin formation in Buruli ulcer lesions.PLoS pathogens · 2022Trial
- A mycobacterial Sec61 inhibitor disrupts lysosome function by blocking Vacuolar-ATPase biosynthesis.European journal of cell biology · 2026Article
- Buruli ulcer.Nature reviews. Disease primers · 2025Review
- Article
- SEC61G promotes colorectal cancer progression by regulating cytosolic CaJournal of gastroenterology · 2025Article
- Cotranslational membrane insertion of the voltage-sensitive KProceedings of the National Academy of Sciences of the United States of America · 2025Article
- TheeLife · 2025Article
- Toward Understanding the Mechanism of Client-Selective Small Molecule Inhibitors of the Sec61 Translocon.Journal of molecular recognition : JMR · 2025Review
- Review
- Mycolactone causes destructive Sec61-dependent loss of the endothelial glycocalyx and vessel basement membrane: a new indirect mechanism driving tissue necrosis inbioRxiv : the preprint server for biology · 2024Article
- Diastereomers of Coibamide A Show Altered Sec61 Client Selectivity and Ligand-Dependent Activity against Patient-Derived Glioma Stem-like Cells.ACS pharmacology & translational science · 2024Article
- Characterization of the interaction between the Sec61 translocon complex and ppαF using optical tweezers.Protein science : a publication of the Protein Society · 2024Article
- Lipid scrambling is a general feature of protein insertases.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Molecular view of ER membrane remodeling by the Sec61/TRAP translocon.EMBO reports · 2023Article
- Signal peptide mimicry primes Sec61 for client-selective inhibition.Nature chemical biology · 2023Article
- Lipid scrambling is a general feature of protein insertases.bioRxiv : the preprint server for biology · 2023Article
- A common mechanism of Sec61 translocon inhibition by small molecules.Nature chemical biology · 2023Article
- Article
- Structural insights into TRAP association with ribosome-Sec61 complex and translocon inhibition by a CADA derivative.Science advances · 2023Article
- Mechanism of Protein Translocation by the Sec61 Translocon Complex.Cold Spring Harbor perspectives in biology · 2023Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Protein secretion in eukaryotes and prokaryotes involves a universally conserved protein translocation channel formed by the Sec61 complex. Unrelated small-molecule natural products and synthetic compounds inhibit Sec61 with differential effects for different substrates or for Sec61 from different organisms, making this a promising target for therapeutic intervention. To understand the mode of inhibition and provide insight into the molecular mechanism of this dynamic translocon, we determined the structure of mammalian Sec61 inhibited by the Mycobacterium ulcerans exotoxin mycolactone via electron cryo-microscopy. Unexpectedly, the conformation of inhibited Sec61 is optimal for substrate engagement, with mycolactone wedging open the cytosolic side of the lateral gate. The inability of mycolactone-inhibited Sec61 to effectively transport substrate proteins implies that signal peptides and transmembrane domains pass through the site occupied by mycolactone. This provides a foundation for understanding the molecular mechanism of Sec61 inhibitors and reveals novel features of translocon function and dynamics.
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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.