Why is cholesterol amphipathic

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Find more information on the Altmetric Attention Score and how the score is calculated. Lipid Res. Circular dichroism CD spectra of the peptide indicated a similar helical structure formation in LUV with and without Chol.

The fluorescence spectral shift, quantum yield, anisotropy, and acrylamide-quenching of the peptide Trp indicated that in PC:Chol LUV, AcA-NH 2 was located in a more polar membrane environment with increased motional freedom and greater accessibility to the aqueous medium. Fluorescence energy transfer from the Trp indole ring to acceptors situated at different depths in the bilayers revealed that the amphipathic peptide penetrated the hydrophobic interior of PC bilayers, while the peptide was located at the polar zwitterionic surface in PC:Chol LUV.

The inclusion of Chol causes the headgroup separation of PC at the surface of LUV and increases the binding maximum of the wedge-shaped amphipathic peptide without disrupting the membrane structure.

In addition, the rigidifying effect of Chol on PC acyl chains prevents the penetration of the peptide into the bilayer interior. These findings imply that Chol in membranes affects the binding and motional freedom of exchangeable plasma apolipoproteins containing class A amphipathic sequences, e. View Author Information. Cite this: Biochemistry , 41 , 12 , — Article Views Altmetric -.

Citations Kharkov National University. Cited By. This article is cited by 29 publications. Madsen, Frederic St. Jackson, Matthew D. This is usually not the case for non-annular lipids that are less or not accessible at all to surrounding membrane lipids.

Indeed, non-annular binding sites may involve several TM domains that form a 3D binding site for the lipid. This has enabled determination of the stoichiometry of the lipid—protein interaction, the selectivity of the protein for different lipids and the amino acid residues physically involved in lipid binding.

X-ray crystallography is of particular value since it can give a precise description of lipid-protein contacts at the atomic scale. Unfortunately, very few 3D structures of protein-cholesterol complexes are available in the literature. In , Hanson et al. Among these domains, TM2 and TM4 appeared particularly critical for cholesterol binding. Interestingly, TM4 contains an aromatic tryptophan residue W that is highly conserved among human G-protein coupled receptors. The aromatic side chain of W stacks onto cholesterol through a CH-Pi interaction with ring D of the sterol.

The binding site also involves two other amino acid residues of TM4 R and L and a second aromatic residue located in TM2 Tyr As noted by Hanson et al.

However, this sequence does not fulfill the criteria of the CRAC domain. Finally, the unique spatial distribution of amino acid residues that are important for cholesterol interaction was used to define a consensus 3D binding motif among human G-protein-coupled receptors as follows: [4.

These glycine residues are involved in cholesterol binding, which is chiefly mediated by van der Waals interactions between the apolar moiety of cholesterol and apolar residues within the motif i. At first glance, this review of cholesterol-binding sites encased in TM domains of proteins may appear rather complex. As a cholesterol-binding domain present in a TM domain, CARC appears more consistent than CRAC in predicting cholesterol-recognition motifs in integral membrane proteins, especially for predicting cholesterol-binding sites located in the exofacial leaflet of the plasma membrane.

Finally non-annular cholesterol-binding sites can be formed by the cooperation of several TM domains of G-protein coupled receptors, rendering the prediction of such binding domains particularly difficult. Linear and 3D binding sites for cholesterol might have distinct biological functions. In bringing together several TM domains, cholesterol could exert a condensing effect on the whole protein, which, e. In contrast, cholesterol interacting with only one TM domain at the periphery of a receptor protein would be more suited to bringing together two distinct receptor macromolecules and triggering their dimerization, a key step in signal transduction cascades Figure 3C.

This may explain why various types of cholesterol-binding motifs can be found in TM domains. Nevertheless, common molecular mechanisms seem to control the interaction of transmembrane proteins with cholesterol. These mechanisms include the delineation of a polar area to accommodate the OH group of cholesterol at the membrane-water interface, and the establishment of numerous van der Waals interactions in the apolar zone of the membrane Epand et al.

London forces require an optimal geometric fit between cholesterol and the apolar side chains of the amino acid residues that belong to the motif. This explains why branched amino acid residues such as Ile, Val, and Leu are overrepresented in cholesterol-binding sites. These simple biochemical rules probably apply to most if not all cholesterol-binding sites that are part of TM domains of proteins. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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CrossRef Full Text. Epand, R. Juxtamembrane protein segments that contribute to recruitment of cholesterol into domains. Biochemistry 45, — Cholesterol and the interaction of proteins with membrane domains. Lipid Res. Cholesterol interaction with proteins that partition into membrane domains: an overview. Fantini, J. Homeostasis Higher Level 7: Nucleic Acids 1. DNA Structure 2. Transcription 3. Translation 8: Metabolism 1. Metabolism 2. Cell Respiration 3.

Photosynthesis 9: Plant Biology 1. Xylem Transport 2. Phloem Transport 3. Plant Growth 4. Plant Reproduction Genetics 1. Meiosis 2. Inheritance 3. Steady-state fluorescence anisotropy of n -AS was also performed to evaluate the acyl chain fluidity in emulsion surface monolayers. Chol decreased the fluorescence lifetime of dansyl-PE and increased the lifetimes and anisotropy values of n -AS. These results demonstrated that Chol alters the surface properties of emulsions, i.

From these results, the charge distribution of the amphipathic helices is suggested to be a determining factor in their response to Chol enrichment in emulsions. B , , 1 , View Author Information. Cite this: J. B , , 1 , — Article Views