ArticleProceedings of the National Academy of Sciences of the United States of America2009
Structural imperatives impose diverse evolutionary constraints on helical membrane proteins.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. 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, 74 citations in OpenAlex.
- Packing of apolar amino acids is not a strong stabilizing force in transmembrane helix dimerization.Biophysical journal · 2025Article
- Co-evolution of alpha-helical transmembrane protein residues: large-scale variant profiling and complete mutational landscape of 2277 known PDB entries representing 504 unique human protein sequences.Journal of molecular evolution · 2025Article
- The lipid bilayer strengthens the cooperative network of membrane proteins.Science advances · 2025Article
- Kingdom-specific lipid unsaturation calibrates sequence evolution in membrane arm subunits of eukaryotic respiratory complexes.Nature communications · 2025Article
- Protein Design: From the Aspect of Water Solubility and Stability.Chemical reviews · 2022Review
- How physical forces drive the process of helical membrane protein folding.EMBO reports · 2022Review
- The Conserved Serine Transporter SdaC Moonlights To Enable Self Recognition.Journal of bacteriology · 2022Article
- Altering CLC stoichiometry by reducing non-polar side-chains at the dimerization interface.Journal of molecular biology · 2021Article
- Transmembrane Helices Are an Over-Presented and Evolutionarily Conserved Source of Major Histocompatibility Complex Class I and II Epitopes.Frontiers in immunology · 2021Article
- Article
- Structural cavities are critical to balancing stability and activity of a membrane-integral enzyme.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Review
- Genetic intolerance analysis as a tool for protein science.Biochimica et biophysica acta. Biomembranes · 2020Review
- Packing of apolar side chains enables accurate design of highly stable membrane proteins.Science (New York, N.Y.) · 2019Article
- Prediction of disease-associated mutations in the transmembrane regions of proteins with known 3D structure.PloS one · 2019Article
- Accurate computational design of multipass transmembrane proteins.Science (New York, N.Y.) · 2018Article
- Design of self-assembling transmembrane helical bundles to elucidate principles required for membrane protein folding and ion transport.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2017Review
- Systematic Analyses and Prediction of Human Drug Side Effect Associated Proteins from the Perspective of Protein Evolution.Genome biology and evolution · 2017Article
- Membrane Proteins Are Dramatically Less Conserved than Water-Soluble Proteins across the Tree of Life.Molecular biology and evolution · 2016Article
- Reversible Unfolding of Rhomboid Intramembrane Proteases.Biophysical journal · 2016Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The amino acid sequences of transmembrane regions of helical membrane proteins are highly constrained, diverging at slower rates than their extramembrane regions and than water-soluble proteins. Moreover, helical membrane proteins seem to fall into fewer families than water-soluble proteins. The reason for the differential restrictions on sequence remains unexplained. Here, we show that the evolution of transmembrane regions is slowed by a previously unrecognized structural constraint: Transmembrane regions bury more residues than extramembrane regions and soluble proteins. This fundamental feature of membrane protein structure is an important contributor to the differences in evolutionary rate and to an increased susceptibility of the transmembrane regions to disease-causing single-nucleotide polymorphisms.
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