ArticleThe Journal of biological chemistry2012
The cytosolic GH loop regulates the phosphatidylinositol 4,5-bisphosphate-induced gating kinetics of Kir2 channels.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- From Crosstalk to Synergism: The Combined Effect of Cholesterol and PI(4,5)PAdvances in experimental medicine and biology · 2023Review
- Cryo-electron microscopy unveils unique structural features of the human Kir2.1 channel.Science advances · 2022Article
- Hypoxia inhibits the cardiaciScience · 2022Article
- Characterization of Lipid-Protein Interactions and Lipid-Mediated Modulation of Membrane Protein Function through Molecular Simulation.Chemical reviews · 2019Review
- Molecular mechanism of phosphoinositides' specificity for the inwardly rectifying potassium channel Kir2.2.Chemical science · 2018Article
- Inward rectifying potassium currents resolved into components: modeling of complex drug actions.Pflugers Archiv : European journal of physiology · 2018Article
- Styrax blocks inward and outward current of Kir2.1 channel.Channels (Austin, Tex.) · 2017Article
- Three pairs of weak interactions precisely regulate the G-loop gate of Kir2.1 channel.Proteins · 2016Article
- Structural Basis for Differences in Dynamics Induced by Leu Versus Ile Residues in the CD Loop of Kir Channels.Molecular neurobiology · 2016Article
- Identification of the Conformational transition pathway in PIP2 Opening Kir Channels.Scientific reports · 2015Article
- Insights into the structural nature of the transition state in the Kir channel gating pathway.Channels (Austin, Tex.) · 2014Article
- A Kir6.2 pore mutation causes inactivation of ATP-sensitive potassium channels by disrupting PIP2-dependent gating.PloS one · 2013Article
- Cholesterol sensitivity of KIR2.1 depends on functional inter-links between the N and C termini.Channels (Austin, Tex.)Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Inwardly rectifying K(+) (Kir) channels set the resting membrane potential and regulate cellular excitability. The activity of Kir channels depends critically on the phospholipid PIP(2). The molecular mechanism by which PIP(2) regulates Kir channel gating is poorly understood. Here, we utilized a combination of computational and electrophysiological approaches to discern structural elements involved in regulating the PIP(2)-induced gating kinetics of Kir2 channels. We identify a novel role for the cytosolic GH loop. Mutations that directly or indirectly affect GH loop flexibility (e.g. V223L, E272G, D292G) increase both the on- and especially the off-gating kinetics. These effects are consistent with a model in which competing interactions between the CD and GH loops for the N terminus regulate the gating of the intracellular G loop gate.
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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.