ArticleBiophysical journal2018
Molecular Dynamics Simulations of Kir2.2 Interactions with an Ensemble of Cholesterol Molecules.
Article in Biophysical journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 58 citations in OpenAlex.
- Structural and functional studies of inward rectifier Kir7.1 and its regulation by the Melanocortin-4 receptor.Nature communications · 2026Article
- Mapping structural and dynamic divergence across the MBOAT family.Structure (London, England : 1993) · 2024Article
- PIPNature communications · 2024Article
- Cholesterol regulation of mechanosensitive ion channels.Frontiers in cell and developmental biology · 2024Review
- LipIDens: simulation assisted interpretation of lipid densities in cryo-EM structures of membrane proteins.Nature communications · 2023Article
- Facilitation of hERG Activation by Its Blocker: A Mechanism to Reduce Drug-Induced Proarrhythmic Risk.International journal of molecular sciences · 2023Review
- Membrane Cholesterol Interactions with Proteins in Hypercholesterolemia-Induced Endothelial Dysfunction.Current atherosclerosis reports · 2023Review
- Insertion Depth Modulates Protein Kinase C-δ-C1b Domain Interactions with Membrane Cholesterol as Revealed by MD Simulations.International journal of molecular sciences · 2023Article
- Role of Lysosomal Cholesterol in Regulating PI(4,5)PAdvances in experimental medicine and biology · 2023Article
- The role of cholesterol binding in the control of cholesterol by the Scap-Insig system.European biophysics journal : EBJ · 2022Article
- Exploring TRPC3 Interaction with Cholesterol through Coarse-Grained Molecular Dynamics Simulations.Biomolecules · 2022Article
- Cholesterol-induced suppression of Kir2 channels is mediated by decoupling at the inter-subunit interfaces.iScience · 2022Article
- Specific interactions of peripheral membrane proteins with lipids: what can molecular simulations show us?Bioscience reports · 2022Article
- Peptidoglycan biosynthesis is driven by lipid transfer along enzyme-substrate affinity gradients.Nature communications · 2022Article
- The Role of Membrane Lipids in Light-Activation ofBiomolecules · 2022Review
- The Role of Lipids in CRAC Channel Function.Biomolecules · 2022Review
- PyLipID: A Python Package for Analysis of Protein-Lipid Interactions from Molecular Dynamics Simulations.Journal of chemical theory and computation · 2022Article
- Methods for Studying Cholesterol-Dependent Regulation of P2X7 Receptors.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Cholesterol-Induced Suppression of Endothelial Kir Channels Is a Driver of Impairment of Arteriolar Flow-Induced Vasodilation in Humans.Hypertension (Dallas, Tex. : 1979) · 2022Article
- PIPBiophysical journal · 2021Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Cholesterol is a major regulator of multiple types of ion channels, but the specific mechanisms and the dynamics of its interactions with the channels are not well understood. Kir2 channels were shown to be sensitive to cholesterol through direct interactions with "cholesterol-sensitive" regions on the channel protein. In this work, we used Martini coarse-grained simulations to analyze the long (μs) timescale dynamics of cholesterol with Kir2.2 channels embedded into a model membrane containing POPC phospholipid with 30 mol% cholesterol. This approach allows us to simulate the dynamic, unbiased migration of cholesterol molecules from the lipid membrane environment to the protein surface of Kir2.2 and explore the favorability of cholesterol interactions at both surface sites and recessed pockets of the channel. We found that the cholesterol environment surrounding Kir channels forms a complex milieu of different short- and long-term interactions, with multiple cholesterol molecules concurrently interacting with the channel. Furthermore, utilizing principles from network theory, we identified four discrete cholesterol-binding sites within the previously identified cholesterol-sensitive region that exist depending on the conformational state of the channel-open or closed. We also discovered that a twofold decrease in the cholesterol level of the membrane, which we found earlier to increase Kir2 activity, results in a site-specific decrease of cholesterol occupancy at these sites in both the open and closed states: cholesterol molecules at the deepest of these discrete sites shows no change in occupancy at different cholesterol levels, whereas the remaining sites showed a marked decrease in occupancy.
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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.