ArticleThe Journal of membrane biology2015
Influence of Pathogenic Mutations on the Energetics of Translocon-Mediated Bilayer Integration of Transmembrane Helices.
Article in The Journal of membrane biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Article
- Spf1 and Ste24: quality controllers of transmembrane protein topology in the eukaryotic cell.Frontiers in cell and developmental biology · 2023Review
- Towards generalizable predictions for G protein-coupled receptor variant expression.Biophysical journal · 2022Article
- Molecular basis for the evolved instability of a human G-protein coupled receptor.Cell reports · 2021Article
- Ribosome-associated quality control of membrane proteins at the endoplasmic reticulum.Journal of cell science · 2020Review
- Probing biophysical sequence constraints within the transmembrane domains of rhodopsin by deep mutational scanning.Science advances · 2020Article
- Proteomic Analysis Identifies Membrane Proteins Dependent on the ER Membrane Protein Complex.Cell reports · 2019Article
- Lipid-Assisted Membrane Protein Folding and Topogenesis.The protein journal · 2019Review
- Folding and Misfolding of Human Membrane Proteins in Health and Disease: From Single Molecules to Cellular Proteostasis.Chemical reviews · 2019Article
- A network of chaperones prevents and detects failures in membrane protein lipid bilayer integration.Nature communications · 2019Article
- Contribution of Cotranslational Folding Defects to Membrane Protein Homeostasis.Journal of the American Chemical Society · 2019Article
- The Retinitis Pigmentosa-Linked Mutations in Transmembrane Helix 5 of Rhodopsin Disrupt Cellular Trafficking Regardless of Oligomerization State.Biochemistry · 2018Article
- Structurally detailed coarse-grained model for Sec-facilitated co-translational protein translocation and membrane integration.PLoS computational biology · 2017Article
- Dynamic Lipid-dependent Modulation of Protein Topology by Post-translational Phosphorylation.The Journal of biological chemistry · 2017Article
- Conformational Stability and Pathogenic Misfolding of the Integral Membrane Protein PMP22.Journal of the American Chemical Society · 2015Article
- Membrane Protein Folding & Lipid Interactions: Theory & Experiment.The Journal of membrane biology · 2015Article
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2 authors.
Funding
Abstract
Aberrant protein folding and assembly contribute to a number of diseases, and efforts to rationalize how pathogenic mutations cause this phenomenon represent an important imperative in biochemical research. However, for α-helical membrane proteins, this task is complicated by the fact that membrane proteins require intricate machinery to achieve structural and functional maturity under cellular conditions. In this work, we utilized the ΔG predictor algorithm ( www.dgpred.cbr.su.se ) to survey 470 known pathogenic mutations occurring in five misfolding-prone α-helical membrane proteins for their predicted effects on the translocon-mediated membrane integration of transmembrane helices, a critical step in biosynthesis and folding of nascent membrane proteins. The results suggest that about 10 % of these mutations are likely to have adverse effects on the topogenesis of nascent membrane proteins. These results suggest that the misfolding of a modest but nonetheless significant subset of pathogenic variants may begin at the translocon. Potential implications for therapeutic design and personalized medicine are discussed.
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