ArticleProceedings of the National Academy of Sciences of the United States of America2008
Direct analysis of cooperativity in multisubunit allosteric proteins.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed.
- Trans-interface coupling in the tetrameric enzyme underlies allosteric control inJournal of structural biology: X · 2026Article
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- Two-colour single-molecule photoinduced electron transfer fluorescence imaging microscopy of chaperone dynamics.Nature communications · 2021Article
- Fragment-Based Local Coupled Cluster Embedding Approach for the Quantification and Analysis of Noncovalent Interactions: Exploring the Many-Body Expansion of the Local Coupled Cluster Energy.Journal of chemical theory and computation · 2021Article
- Rational design to control the trade-off between receptor affinity and cooperativity.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Inactivation gating of Kv7.1 channels does not involve concerted cooperative subunit interactions.Channels (Austin, Tex.) · 2018Article
- High-Dimensional Mutant and Modular Thermodynamic Cycles, Molecular Switching, and Free Energy Transduction.Annual review of biophysics · 2017Review
- Intra- and Intersubunit Dynamic Binding in Kv4.2 Channel Closed-State Inactivation.Biophysical journal · 2016Article
- Intersubunit Concerted Cooperative and cis-Type Mechanisms Modulate Allosteric Gating in Two-Pore-Domain Potassium Channel TREK-2.Frontiers in cellular neuroscience · 2016Article
- Molecular pathophysiology and pharmacology of the voltage-sensing module of neuronal ion channels.Frontiers in cellular neuroscience · 2015Review
- A self-consistent approach for determining pairwise interactions that underlie channel activation.The Journal of general physiology · 2014Article
- Cooperative subunit interactions mediate fast C-type inactivation of hERG1 K+ channels.The Journal of physiology · 2014Article
- Concerted all-or-none subunit interactions mediate slow deactivation of human ether-à-go-go-related gene K+ channels.The Journal of biological chemistry · 2014Article
- Modeling ion channels: past, present, and future.The Journal of general physiology · 2014Review
- Signal transmission within the P2X2 trimeric receptor.The Journal of general physiology · 2014Article
- Stoichiometry of altered hERG1 channel gating by small molecule activators.The Journal of general physiology · 2014Article
- Using hierarchical thermodynamic linkage analysis to study ion channel gating.The Journal of general physiology · 2013Article
- Probing the energy landscape of activation gating of the bacterial potassium channel KcsA.PLoS computational biology · 2013Article
- A linkage analysis toolkit for studying allosteric networks in ion channels.The Journal of general physiology · 2013Article
- Tetrameric assembly of KvLm K+ channels with defined numbers of voltage sensors.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
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4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Allosteric regulation of protein function is a fundamental phenomenon of major importance in many cellular processes. Such regulation is often achieved by ligand-induced conformational changes in multimeric proteins that may give rise to cooperativity in protein function. At the heart of allosteric mechanisms offered to account for such phenomenon, involving either concerted or sequential conformational transitions, lie changes in intersubunit interactions along the ligation pathway of the protein. However, structure-function analysis of such homooligomeric proteins by means of mutagenesis, although it provides valuable indirect information regarding (allosteric) mechanisms of action, it does not define the contribution of individual subunits nor interactions thereof to cooperativity in protein function, because any point mutation introduced into homooligomeric proteins will be present in all subunits. Here, we present a general strategy for the direct analysis of cooperativity in multisubunit proteins that combines measurement of the effects on protein function of all possible combinations of mutated subunits with analysis of the hierarchy of intersubunit interactions, assessed by using high-order double-mutant cycle-coupling analysis. We show that the pattern of high-order intersubunit coupling can serve as a discriminative criterion for defining concerted versus sequential conformational transitions underlying protein function. This strategy was applied to the particular case of the voltage-activated potassium channel protein (Kv) to provide compelling evidence for a concerted all-or-none activation gate opening of the Kv channel pore domain. An direct and detailed analysis of the contribution of high-order intersubunit interactions to cooperativity in the function of an allosteric protein has not previously been presented.
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