ArticleeLife2015
Regulation of multispanning membrane protein topology via post-translational annealing.
Article in eLife, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed.
- Membrane Protein Insertion in Cells: Principles, Pathways, and Quality Control.Chemical reviews · 2026Review
- The lipid bilayer strengthens the cooperative network of membrane proteins.Science advances · 2025Article
- Cotranslational membrane insertion of the voltage-sensitive KProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Steric trapping strategy for studying the folding of helical membrane proteins.Methods (San Diego, Calif.) · 2024Review
- Still rocking in the structural era: A molecular overview of the small multidrug resistance (SMR) transporter family.The Journal of biological chemistry · 2022Review
- The Tiny Companion Matters: The Important Role of Protons in Active Transports in Plants.International journal of molecular sciences · 2022Review
- How physical forces drive the process of helical membrane protein folding.EMBO reports · 2022Review
- Untangling the complexity of membrane protein folding.Current opinion in structural biology · 2022Review
- Lipid bilayer induces contraction of the denatured state ensemble of a helical-bundle membrane protein.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Folding and Insertion of Transmembrane Helices at the ER.International journal of molecular sciences · 2021Review
- Article
- Atomistic mechanism of transmembrane helix association.PLoS computational biology · 2020Article
- Cotranslational folding stimulates programmed ribosomal frameshifting in the alphavirus structural polyprotein.The Journal of biological chemistry · 2020Article
- Dynamics of Co-translational Membrane Protein Integration and Translocation via the Sec Translocon.Journal of the American Chemical Society · 2020Review
- Watching helical membrane proteins fold reveals a common N-to-C-terminal folding pathway.Science (New York, N.Y.) · 2019Article
- Dynamic membrane topology in an unassembled membrane protein.Nature chemical biology · 2019Article
- Emerging Diversity in Lipid-Protein Interactions.Chemical reviews · 2019Review
- Folding and Misfolding of Human Membrane Proteins in Health and Disease: From Single Molecules to Cellular Proteostasis.Chemical reviews · 2019Article
- Contribution of Cotranslational Folding Defects to Membrane Protein Homeostasis.Journal of the American Chemical Society · 2019Article
- Energy landscape underlying spontaneous insertion and folding of an alpha-helical transmembrane protein into a bilayer.Nature communications · 2018Article
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Authors and funding
3 authors.
Funding
Abstract
The canonical mechanism for multispanning membrane protein topogenesis suggests that protein topology is established during cotranslational membrane integration. However, this mechanism is inconsistent with the behavior of EmrE, a dual-topology protein for which the mutation of positively charged loop residues, even close to the C-terminus, leads to dramatic shifts in its topology. We use coarse-grained simulations to investigate the Sec-facilitated membrane integration of EmrE and its mutants on realistic biological timescales. This work reveals a mechanism for regulating membrane-protein topogenesis, in which initially misintegrated configurations of the proteins undergo post-translational annealing to reach fully integrated multispanning topologies. The energetic barriers associated with this post-translational annealing process enforce kinetic pathways that dictate the topology of the fully integrated proteins. The proposed mechanism agrees well with the experimentally observed features of EmrE topogenesis and provides a range of experimentally testable predictions regarding the effect of translocon mutations on membrane protein topogenesis.
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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.