ArticleProteins2009
Binding and release of cholesterol in the Osh4 protein of yeast.
Article in Proteins, 2009. 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, 34 citations in OpenAlex.
- Allosterically coupled conformational dynamics in solution prepare the sterol transfer protein StarD4 to release its cargo upon interaction with target membranes.Frontiers in molecular biosciences · 2023Article
- Functional analyses of phosphatidylserine/PI(4)P exchangers with diverse lipid species and membrane contexts reveal unanticipated rules on lipid transfer.BMC biology · 2021Article
- Mechanisms of nonvesicular lipid transport.The Journal of cell biology · 2021Review
- Article
- Characterization of Lipid-Protein Interactions and Lipid-Mediated Modulation of Membrane Protein Function through Molecular Simulation.Chemical reviews · 2019Review
- A search for ceramide binding proteins using bifunctional lipid analogs yields CERT-related protein StarD7.Journal of lipid research · 2018Article
- A cholesterol recognition motif in human phospholipid scramblase 1.Biophysical journal · 2014Article
- Web-based computational chemistry education with CHARMMing I: Lessons and tutorial.PLoS computational biology · 2014Article
- Bexarotene blocks calcium-permeable ion channels formed by neurotoxic Alzheimer's β-amyloid peptides.ACS chemical neuroscience · 2014Article
- Biochemical identification of a linear cholesterol-binding domain within Alzheimer's β amyloid peptide.ACS chemical neuroscience · 2013Article
- Cholesterol accelerates the binding of Alzheimer's β-amyloid peptide to ganglioside GM1 through a universal hydrogen-bond-dependent sterol tuning of glycolipid conformation.Frontiers in physiology · 2013Article
- The oxysterol-binding protein superfamily: new concepts and old proteins.Biochemical Society transactions · 2012Review
- Steered molecular dynamics simulations of ligand-receptor interaction in lipocalins.European biophysics journal : EBJ · 2011Article
- Disclosure of cholesterol recognition motifs in transmembrane domains of the human nicotinic acetylcholine receptor.Scientific reports · 2011Article
- The diverse functions of oxysterol-binding proteins.Annual review of cell and developmental biology · 2010Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Sterols have been shown experimentally to bind to the Osh4 protein (a homolog of the oxysterol binding proteins) of Saccharomyces cerevisiae within a binding tunnel, which consists of antiparallel beta-sheets that resemble a beta-barrel and three alpha-helices of the N-terminus. This and other Osh proteins are essential for intracellular transport of sterols and ultimately cell life. Molecular dynamics (MD) simulations are used to study the binding of cholesterol to Osh4 at the atomic level. The structure of the protein is stable during the course of all MD simulations and has little deviation from the experimental crystal structure. The conformational stability of cholesterol within the binding tunnel is aided in part by direct or water-mediated interactions between the 3-hydroxyl (3-OH) group of cholesterol and Trp(46), Gln(96), Tyr(97), Asn(165), and/or Gln(181) as well as dispersive interactions with Phe(42), Leu(24), Leu(39), Ile(167), and Ile(203). These residues along with other nonpolar residues in the binding tunnel and lid contribute nearly 75% to the total binding energy. The strongest and most populated interaction is between Gln(96) and 3-OH with a cholesterol/Gln(96) interaction energy of -4.5 +/- 1.0 kcal/mol. Phe(42) has a similar level of attraction to cholesterol with -4.1 +/- 0.3 kcal/mol. A MD simulation without the N-terminus lid that covers the binding tunnel resulted in similar binding conformations and binding energies when compared with simulations with the full-length protein. Steered MD was used to determine details of the mechanism used by Osh4 to release cholesterol to the cytoplasm. Phe(42), Gln(96), Asn(165), Gln(181), Pro(211), and Ile(206) are found to direct the cholesterol as it exits the binding tunnel as well as Lys(109). The mechanism of sterol release is conceptualized as a molecular ladder with the rungs being amino acids or water-mediated amino acids that interact with 3-OH.
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Registered trials
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