ArticleBiochimica et biophysica acta2011
Lipid-binding surfaces of membrane proteins: evidence from evolutionary and structural analysis.
Article in Biochimica et biophysica acta, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed.
- Current achievements, strategies, obstacles, and overcoming the challenges of the protein engineering in Pichia pastoris expression system.World journal of microbiology & biotechnology · 2023Review
- Constructing Nanocaged Enzymes for Synergistic Catalysis of COAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Cholesterol in Class C GPCRs: Role, Relevance, and Localization.Membranes · 2023Article
- Docking cholesterol to integral membrane proteins with Rosetta.PLoS computational biology · 2023Article
- Cholesterol Dependent Activity of the Adenosine AMolecules (Basel, Switzerland) · 2022Article
- Overview on solubilization and lipid reconstitution of Na,K-ATPase: enzyme kinetic and biophysical characterization.Biophysical reviews · 2020Review
- In Silico Structure and Sequence Analysis of Bacterial Porins and Specific Diffusion Channels for Hydrophilic Molecules: Conservation, Multimericity and Multifunctionality.International journal of molecular sciences · 2016Article
- CLD1 Reverses the Ubiquinone Insufficiency of Mutant cat5/coq7 in a Saccharomyces cerevisiae Model System.PloS one · 2016Article
- Effect of high-fat diet on cholesterol metabolism in rats and its association with Na⁺/K⁺-ATPase/Src/pERK signaling pathway.Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban · 2015Article
- Modulation of plasma membrane Ca2+-ATPase by neutral phospholipids: effect of the micelle-vesicle transition and the bilayer thickness.The Journal of biological chemistry · 2015Article
- Stimulation, inhibition, or stabilization of Na,K-ATPase caused by specific lipid interactions at distinct sites.The Journal of biological chemistry · 2015Article
- Computational modeling of membrane proteins.Proteins · 2015Review
- Structural and functional assessment of perilipin 2 lipid binding domain(s).Biochemistry · 2014Article
- Life at the border: adaptation of proteins to anisotropic membrane environment.Protein science : a publication of the Protein Society · 2014Review
- Protein expression in Pichia pastoris: recent achievements and perspectives for heterologous protein production.Applied microbiology and biotechnology · 2014Review
- Weakly stable regions and protein-protein interactions in beta-barrel membrane proteins.Current pharmaceutical design · 2014Review
- Atox1 contains positive residues that mediate membrane association and aid subsequent copper loading.The Journal of membrane biology · 2013Article
- An analysis of oligomerization interfaces in transmembrane proteins.BMC structural biology · 2013Article
- Neutral phospholipids stimulate Na,K-ATPase activity: a specific lipid-protein interaction.The Journal of biological chemistry · 2013Article
- Ligand-dependent cholesterol interactions with the human A(2A) adenosine receptor.Chemistry and physics of lipids · 2013Article
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3 authors.
Funding
Abstract
Membrane proteins function in the diverse environment of the lipid bilayer. Experimental evidence suggests that some lipid molecules bind tightly to specific sites on the membrane protein surface. These lipid molecules often act as co-factors and play important functional roles. In this study, we have assessed the evolutionary selection pressure experienced at lipid-binding sites in a set of α-helical and β-barrel membrane proteins using posterior probability analysis of the ratio of synonymous vs. nonsynonymous substitutions (ω-ratio). We have also carried out a geometric analysis of the membrane protein structures to identify residues in close contact with co-crystallized lipids. We found that residues forming cholesterol-binding sites in both β(2)-adrenergic receptor and Na(+)-K(+)-ATPase exhibit strong conservation, which can be characterized by an expanded cholesterol consensus motif for GPCRs. Our results suggest the functional importance of aromatic stacking interactions and interhelical hydrogen bonds in facilitating protein-cholesterol interactions, which is now reflected in the expanded motif. We also find that residues forming the cardiolipin-binding site in formate dehydrogenase-N γ-subunit and the phosphatidylglycerol binding site in KcsA are under strong purifying selection pressure. Although the lipopolysaccharide (LPS)-binding site in ferric hydroxamate uptake receptor (FhuA) is only weakly conserved, we show using a statistical mechanical model that LPS binds to the least stable FhuA β-strand and protects it from the bulk lipid. Our results suggest that specific lipid binding may be a general mechanism employed by β-barrel membrane proteins to stabilize weakly stable regions. Overall, we find that the residues forming specific lipid binding sites on the surfaces of membrane proteins often experience strong purifying selection pressure.
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