ArticleThe Journal of cell biology2012
A gating motif in the translocation channel sets the hydrophobicity threshold for signal sequence function.
Article in The Journal of cell biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 62 citations in OpenAlex.
- Toward Understanding the Mechanism of Client-Selective Small Molecule Inhibitors of the Sec61 Translocon.Journal of molecular recognition : JMR · 2025Review
- Article
- Signal peptide mimicry primes Sec61 for client-selective inhibition.Nature chemical biology · 2023Article
- A common mechanism of Sec61 translocon inhibition by small molecules.Nature chemical biology · 2023Article
- A selectivity filter in the ER membrane protein complex limits protein misinsertion at the ER.The Journal of cell biology · 2023Article
- Mechanism of Protein Translocation by the Sec61 Translocon Complex.Cold Spring Harbor perspectives in biology · 2023Review
- Cell-Free Expression to Probe Co-Translational Insertion of an Alpha Helical Membrane Protein.Frontiers in molecular biosciences · 2022Article
- Cancer associated mutations in Sec61γ alter the permeability of the ER translocase.PLoS genetics · 2021Article
- Ipomoeassin-F disrupts multiple aspects of secretory protein biogenesis.Scientific reports · 2021Article
- Complexity and Specificity of Sec61-Channelopathies: Human Diseases Affecting Gating of the Sec61 Complex.Cells · 2021Review
- How does Sec63 affect the conformation of Sec61 in yeast?PLoS computational biology · 2021Article
- A ribosome-associated chaperone enables substrate triage in a cotranslational protein targeting complex.Nature communications · 2020Article
- Structure of the Inhibited State of the Sec Translocon.Molecular cell · 2020Article
- Dynamics of Co-translational Membrane Protein Integration and Translocation via the Sec Translocon.Journal of the American Chemical Society · 2020Review
- Pre-emptive Quality Control of a Misfolded Membrane Protein by Ribosome-Driven Effects.Current biology : CB · 2020Article
- The conserved C-terminus of Sss1p is required to maintain the endoplasmic reticulum permeability barrier.The Journal of biological chemistry · 2020Article
- Asparagine-linked glycosylation is not directly coupled to protein translocation across the endoplasmic reticulum inMolecular biology of the cell · 2019Article
- Structure of the posttranslational Sec protein-translocation channel complex from yeast.Science (New York, N.Y.) · 2019Article
- Forces on Nascent Polypeptides during Membrane Insertion and Translocation via the Sec Translocon.Biophysical journal · 2018Article
- Interaction mapping of the Sec61 translocon identifies two Sec61α regions interacting with hydrophobic segments in translocating chains.The Journal of biological chemistry · 2018Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
A critical event in protein translocation across the endoplasmic reticulum is the structural transition between the closed and open conformations of Sec61, the eukaryotic translocation channel. Channel opening allows signal sequence insertion into a gap between the N- and C-terminal halves of Sec61. We have identified a gating motif that regulates the transition between the closed and open channel conformations. Polar amino acid substitutions in the gating motif cause a gain-of-function phenotype that permits translocation of precursors with marginally hydrophobic signal sequences. In contrast, hydrophobic substitutions at certain residues in the gating motif cause a protein translocation defect. We conclude that the gating motif establishes the hydrophobicity threshold for functional insertion of a signal sequence into the Sec61 complex, thereby allowing the wild-type translocation channel to discriminate between authentic signal sequences and the less hydrophobic amino acid segments in cytosolic proteins. Bioinformatic analysis indicates that the gating motif is conserved between eubacterial and archaebacterial SecY and eukaryotic Sec61.
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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.