ArticleThe Journal of experimental medicine2016
Mycolactone subverts immunity by selectively blocking the Sec61 translocon.
Article in The Journal of experimental medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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Who cites it
84 citing papers in PubMed, 131 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
- Advances in SEC61G research: from ER translocon subunit to emerging pan-cancer oncogenic roles.Cancer biology & therapy · 2026Review
- A mycobacterial Sec61 inhibitor disrupts lysosome function by blocking Vacuolar-ATPase biosynthesis.European journal of cell biology · 2026Article
- Accelerating vaccine research and development for skin neglected tropical diseases: A case for leishmaniasis, leprosy, and Buruli ulcer.PLoS neglected tropical diseases · 2026Review
- SEC61: a potential therapeutic target in transplantation.Frontiers in immunology · 2026Review
- Buruli ulcer.Nature reviews. Disease primers · 2025Review
- Successful treatment with joint retention of Mycobacterium ulcerans prosthetic joint infection in a patient with rheumatoid arthritis.PLoS neglected tropical diseases · 2025Article
- Article
- Rules of Engagement for Components of Membrane Protein Biogenesis at the Human Endoplasmic Reticulum.International journal of molecular sciences · 2025Review
- TheeLife · 2025Article
- A composite subunit vaccine confers full protection against Buruli ulcer disease in the mouse footpad model of Mycobacterium ulcerans infection.PLoS neglected tropical diseases · 2025Article
- Toward Understanding the Mechanism of Client-Selective Small Molecule Inhibitors of the Sec61 Translocon.Journal of molecular recognition : JMR · 2025Review
- Exploring the ER channel protein Sec61: recent advances in pathophysiological significance and novel pharmacological inhibitors.Frontiers in pharmacology · 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
- Inflammasome-triggered IL-18 controls skin inflammation in the progression of Buruli ulcer.PLoS pathogens · 2023Article
- Design of Synthetic Surrogates for the Macrolactone Linker Motif in Coibamide A.ACS medicinal chemistry letters · 2023Article
- A common mechanism of Sec61 translocon inhibition by small molecules.Nature chemical biology · 2023Article
24 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mycolactone, an immunosuppressive macrolide released by the human pathogen Mycobacterium ulcerans, was previously shown to impair Sec61-dependent protein translocation, but the underlying molecular mechanism was not identified. In this study, we show that mycolactone directly targets the α subunit of the Sec61 translocon to block the production of secreted and integral membrane proteins with high potency. We identify a single-amino acid mutation conferring resistance to mycolactone, which localizes its interaction site near the lumenal plug of Sec61α. Quantitative proteomics reveals that during T cell activation, mycolactone-mediated Sec61 blockade affects a selective subset of secretory proteins including key signal-transmitting receptors and adhesion molecules. Expression of mutant Sec61α in mycolactone-treated T cells rescued their homing potential and effector functions. Furthermore, when expressed in macrophages, the mycolactone-resistant mutant restored IFN-γ receptor-mediated antimicrobial responses. Thus, our data provide definitive genetic evidence that Sec61 is the host receptor mediating the diverse immunomodulatory effects of mycolactone and identify Sec61 as a novel regulator of immune cell functions.
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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.