ArticleThe Journal of general physiology2014
Evolutionary imprint of activation: the design principles of VSDs.
Article in The Journal of general physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed.
- Voltage-sensing domains: structural and functional diversity.European biophysics journal : EBJ · 2026Review
- GORK KNature communications · 2025Article
- Voltage sensors.Molecular pharmacology · 2025Review
- 3D-aligned tetrameric ion channels with universal residue labels for comparative structural analysis.Biophysical journal · 2025Article
- Dual mechanisms contribute to enhanced voltage dependence of an electric fish potassium channel.Biophysical journal · 2024Article
- Dynamics of activation in the voltage-sensing domain of Ciona intestinalis phosphatase Ci-VSP.Nature communications · 2024Article
- Anionic omega currents from single countercharge mutants in the voltage-sensing domain of Ci-VSP.The Journal of general physiology · 2024Article
- Exploring Flexibility and Folding Patterns Throughout Time in Voltage Sensors.Journal of molecular evolution · 2023Article
- Article
- Engineering a KNature plants · 2022Article
- Mechanism of voltage gating in the voltage-sensing phosphatase Ci-VSP.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Sustained deep-tissue voltage recording using a fast indicator evolved for two-photon microscopy.Cell · 2022Article
- Complex effects on CaScientific reports · 2022Article
- Evolutionary coupling analysis guides identification of mistrafficking-sensitive variants in cardiac KFrontiers in pharmacology · 2022Article
- Charge substitutions at the voltage-sensing module of domain III enhance actions of site-3 and site-4 toxins on an insect sodium channel.Insect biochemistry and molecular biology · 2021Article
- Evolutionarily Conserved Interactions within the Pore Domain of Acid-Sensing Ion Channels.Biophysical journal · 2020Article
- Roles for Countercharge in the Voltage Sensor Domain of Ion Channels.Frontiers in pharmacology · 2020Review
- Voltage-gated Sodium Channels and Blockers: An Overview and Where Will They Go?Current medical science · 2019Review
- Voltage vs. Ligand I: Structural basis of the intrinsic flexibility of S3 segment and its significance in ion channel activation.Channels (Austin, Tex.) · 2019Article
- Voltage vs. Ligand II: Structural insights of the intrinsic flexibility in cyclic nucleotide-gated channels.Channels (Austin, Tex.) · 2019Article
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4 authors.
Funding
Abstract
Voltage-sensor domains (VSDs) are modular biomolecular machines that transduce electrical signals in cells through a highly conserved activation mechanism. Here, we investigate sequence-function relationships in VSDs with approaches from information theory and probabilistic modeling. Specifically, we collect over 6,600 unique VSD sequences from diverse, long-diverged phylogenetic lineages and relate the statistical properties of this ensemble to functional constraints imposed by evolution. The VSD is a helical bundle with helices labeled S1-S4. Surrounding conserved VSD residues such as the countercharges and the S2 phenylalanine, we discover sparse networks of coevolving residues. Additional networks are found lining the VSD lumen, tuning the local hydrophilicity. Notably, state-dependent contacts and the absence of coevolution between S4 and the rest of the bundle are imprints of the activation mechanism on the VSD sequence ensemble. These design principles rationalize existing experimental results and generate testable hypotheses.
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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.