ArticleeLife2014
An allosteric Sec61 inhibitor traps nascent transmembrane helices at the lateral gate.
Article in eLife, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
55 citing papers in PubMed, 87 citations in OpenAlex.
- SND3 is the membrane insertase within a distinct SEC61 translocon complex.Nature communications · 2025Article
- Rules of Engagement for Components of Membrane Protein Biogenesis at the Human Endoplasmic Reticulum.International journal of molecular sciences · 2025Review
- A light-resuming strategy as a screening method for selecting Sec61 inhibitors down-modulating PD-L1 expression.Nature communications · 2025Article
- Toward Understanding the Mechanism of Client-Selective Small Molecule Inhibitors of the Sec61 Translocon.Journal of molecular recognition : JMR · 2025Review
- Rough microsomes isolated from snap-frozen canine pancreatic tissue retain their co-translational translocation functionality.Biology methods & protocols · 2025Article
- Exploring the ER channel protein Sec61: recent advances in pathophysiological significance and novel pharmacological inhibitors.Frontiers in pharmacology · 2025Review
- Global signal peptide profiling reveals principles of selective Sec61 inhibition.Nature chemical biology · 2024Article
- Marine-Derived Anticancer Agents Targeting Apoptotic Pathways: Exploring the Depths for Novel Cancer Therapies.Marine drugs · 2024Review
- A common mechanism of Sec61 translocon inhibition by small molecules.Nature chemical biology · 2023Article
- Signal peptide mimicry primes Sec61 for client-selective inhibition.Nature chemical biology · 2023Article
- Review
- 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
- The Sec61 translocon is a therapeutic vulnerability in multiple myeloma.EMBO molecular medicine · 2022Article
- Biochemical and Biological Assays of Mycolactone-Mediated Inhibition of Sec61.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Mycolactone enhances the Ca2+ leak from endoplasmic reticulum by trapping Sec61 translocons in a Ca2+ permeable state.The Biochemical journal · 2021Article
- Folding and Insertion of Transmembrane Helices at the ER.International journal of molecular sciences · 2021Review
- Emerging View on the Molecular Functions of Sec62 and Sec63 in Protein Translocation.International journal of molecular sciences · 2021Review
- Inhibitors of the Sec61 Complex and Novel High Throughput Screening Strategies to Target the Protein Translocation Pathway.International journal of molecular sciences · 2021Review
- Complexity and Specificity of Sec61-Channelopathies: Human Diseases Affecting Gating of the Sec61 Complex.Cells · 2021Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Membrane protein biogenesis requires the coordinated movement of hydrophobic transmembrane domains (TMD) from the cytosolic vestibule of the Sec61 channel into the lipid bilayer. Molecular insight into TMD integration has been hampered by the difficulty of characterizing intermediates during this intrinsically dynamic process. In this study, we show that cotransin, a substrate-selective Sec61 inhibitor, traps nascent TMDs in the cytosolic vestibule, permitting detailed interrogation of an early pre-integration intermediate. Site-specific crosslinking revealed the pre-integrated TMD docked to Sec61 near the cytosolic tip of the lateral gate. Escape from cotransin-arrest depends not only on cotransin concentration, but also on the biophysical properties of the TMD. Genetic selection of cotransin-resistant cancer cells uncovered multiple mutations clustered near the lumenal plug of Sec61α, thus revealing cotransin's likely site of action. Our results suggest that TMD/lateral gate interactions facilitate TMD transfer into the membrane, a process that is allosterically modulated by cotransin binding to the plug. DOI: http://dx.doi.org/10.7554/eLife.01483.001.
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What OpenQuestion holds
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.