ArticleBiophysical journal2021
Structural determinants of cholesterol recognition in helical integral membrane proteins.
Article in Biophysical journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
- Membrane Curvature Generation by the Caveolin 8S Complex and the Role of Cholesterol.Journal of chemical theory and computation · 2026Article
- CholBindNet as an interpretable neural network for cholesterol-binding site classification.Communications chemistry · 2026Article
- Membrane Curvature Generation by the Caveolin 8S Complex and the Role of Cholesterol.bioRxiv : the preprint server for biology · 2026Article
- CholBindNet: Interpretable Neural Networks for Cholesterol Binding Site Prediction.bioRxiv : the preprint server for biology · 2026Article
- Physics-based evolution of transmembrane helices reveals mechanisms of cholesterol attraction.Nature communications · 2025Article
- Dishevelled localization and function are differentially regulated by structurally distinct sterols.iScience · 2025Article
- Cholesterol and Lipid Rafts in the Biogenesis of Amyloid-β Protein and Alzheimer's Disease.Annual review of biophysics · 2024Review
- Identification of structural motifs critical for human G6PC2 function informed by sequence analysis and an AlphaFold2-predicted model.Bioscience reports · 2024Article
- Estimating the Cholesterol Affinity of Integral Membrane Proteins from Experimental Data.Biochemistry · 2024Article
- Cholesterol in Class C GPCRs: Role, Relevance, and Localization.Membranes · 2023Article
- Docking cholesterol to integral membrane proteins with Rosetta.PLoS computational biology · 2023Article
- Regulation of membrane protein structure and function by their lipid nano-environment.Nature reviews. Molecular cell biology · 2023Review
- Lipid-Protein Interactions in Plasma Membrane Organization and Function.Annual review of biophysics · 2022Review
- Cholesterol Is a Dose-Dependent Positive Allosteric Modulator of CCR3 Ligand Affinity and G Protein Coupling.Frontiers in molecular biosciences · 2021Article
- Contribution of Membrane Lipids to Postsynaptic Protein Organization.Frontiers in synaptic neuroscience · 2021Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 2 countries.
Funding
Abstract
Cholesterol is an integral component of mammalian membranes. It has been shown to modulate membrane fluidity and dynamics and alter integral membrane protein function. However, understanding the molecular mechanisms of how cholesterol impacts protein function is complicated by limited and conflicting structural data. Because of the nature of the crystallization and cryo-EM structure determination, it is difficult to distinguish between specific and biologically relevant interactions and a nonspecific association. The only widely recognized search algorithm for cholesterol-integral-membrane-protein interaction sites is sequence based, i.e., searching for the so-called "Cholesterol Recognition/interaction Amino acid Consensus" motif. Although these motifs are present in numerous integral membrane proteins, there is inconclusive evidence to support their necessity or sufficiency for cholesterol binding. Here, we leverage the increasing number of experimental cholesterol-integral-membrane-protein structures to systematically analyze putative interaction sites based on their spatial arrangement and evolutionary conservation. This analysis creates three-dimensional representations of general cholesterol interaction sites that form clusters across multiple integral membrane protein classes. We also classify cholesterol-integral-membrane-protein interaction sites as either likely-specific or nonspecific. Information gleaned from our characterization will eventually enable a structure-based approach to predict and design cholesterol-integral-membrane-protein interaction sites.
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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.