22 research outputs found

    The role of hydrophobic interactions in positioning of peripheral proteins in membranes

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    Abstract Background Three-dimensional (3D) structures of numerous peripheral membrane proteins have been determined. Biological activity, stability, and conformations of these proteins depend on their spatial positions with respect to the lipid bilayer. However, these positions are usually undetermined. Results We report the first large-scale computational study of monotopic/peripheral proteins with known 3D structures. The optimal translational and rotational positions of 476 proteins are determined by minimizing energy of protein transfer from water to the lipid bilayer, which is approximated by a hydrocarbon slab with a decadiene-like polarity and interfacial regions characterized by water-permeation profiles. Predicted membrane-binding sites, protein tilt angles and membrane penetration depths are consistent with spin-labeling, chemical modification, fluorescence, NMR, mutagenesis, and other experimental studies of 53 peripheral proteins and peptides. Experimental membrane binding affinities of peripheral proteins were reproduced in cases that did not involve a helix-coil transition, specific binding of lipids, or a predominantly electrostatic association. Coordinates of all examined peripheral proteins and peptides with the calculated hydrophobic membrane boundaries, subcellular localization, topology, structural classification, and experimental references are available through the Orientations of Proteins in Membranes (OPM) database. Conclusion Positions of diverse peripheral proteins and peptides in the lipid bilayer can be accurately predicted using their 3D structures that represent a proper membrane-bound conformation and oligomeric state, and have membrane binding elements present. The success of the implicit solvation model suggests that hydrophobic interactions are usually sufficient to determine the spatial position of a protein in the membrane, even when electrostatic interactions or specific binding of lipids are substantial. Our results demonstrate that most peripheral proteins not only interact with the membrane surface, but penetrate through the interfacial region and reach the hydrocarbon interior, which is consistent with published experimental studies.http://deepblue.lib.umich.edu/bitstream/2027.42/116604/1/12900_2007_Article_125.pd

    OPM database and PPM web server: resources for positioning of proteins in membranes

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    The Orientations of Proteins in Membranes (OPM) database is a curated web resource that provides spatial positions of membrane-bound peptides and proteins of known three-dimensional structure in the lipid bilayer, together with their structural classification, topology and intracellular localization. OPM currently contains more than 1200 transmembrane and peripheral proteins and peptides from approximately 350 organisms that represent approximately 3800 Protein Data Bank entries. Proteins are classified into classes, superfamilies and families and assigned to 21 distinct membrane types. Spatial positions of proteins with respect to the lipid bilayer are optimized by the PPM 2.0 method that accounts for the hydrophobic, hydrogen bonding and electrostatic interactions of the proteins with the anisotropic water-lipid environment described by the dielectric constant and hydrogen-bonding profiles. The OPM database is freely accessible at http://opm.phar.umich.edu. Data can be sorted, searched or retrieved using the hierarchical classification, source organism, localization in different types of membranes. The database offers downloadable coordinates of proteins and peptides with membrane boundaries. A gallery of protein images and several visualization tools are provided. The database is supplemented by the PPM server (http://opm.phar.umich.edu/server.php) which can be used for calculating spatial positions in membranes of newly determined proteins structures or theoretical models

    BIOINFORMATICS APPLICATIONS NOTE doi:10.1093/bioinformatics/btk023 Structural bioinformatics OPM: Orientations of Proteins in Membranes database

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    Summary: The Orientations of Proteins in Membranes (OPM) database providesa collectionof transmembrane, monotopicand peripheral proteins from the Protein Data Bank whose spatial arrangements in the lipid bilayer have been calculated theoretically and compared with experimental data. The databaseallows analysis, sorting and searching of membrane proteins based on their structural classification, species, destination membrane, numbers of transmembrane segments and subunits, numbers of secondary structures and the calculated hydrophobic thickness or tilt angle with respect to the bilayer normal. All coordinate files with the calculated membrane boundaries are available for downloading

    The role of hydrophobic interactions in positioning of peripheral proteins in membranes-9

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    <p><b>Copyright information:</b></p><p>Taken from "The role of hydrophobic interactions in positioning of peripheral proteins in membranes"</p><p>http://www.biomedcentral.com/1472-6807/7/44</p><p>BMC Structural Biology 2007;7():44-44.</p><p>Published online 29 Jun 2007</p><p>PMCID:PMC1934363.</p><p></p> model, respectively. Residues identified as penetrating the non-polar interior of micelles by NMR (and also shown to be important for membrane binding) are colored red. Znions (FYVE domain) are shown as balls colored magenta. Cationic residues involved in ligand and membrane interactions are colored blue. Hydrocarbon core boundary at the cytoplasmic side is indicated by blue dots. The layer of lipid phosphates ("P") is shown by gold dots (at 5 Å outside the hydrocarbon boundary). The center of membrane is indicated by grey dots (at 15 Å inside the boundary)

    The role of hydrophobic interactions in positioning of peripheral proteins in membranes-7

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    <p><b>Copyright information:</b></p><p>Taken from "The role of hydrophobic interactions in positioning of peripheral proteins in membranes"</p><p>http://www.biomedcentral.com/1472-6807/7/44</p><p>BMC Structural Biology 2007;7():44-44.</p><p>Published online 29 Jun 2007</p><p>PMCID:PMC1934363.</p><p></p>models, respectively. Caions are shown as balls colored magenta. Residues identified as penetrating to a non-polar environment by SDSL are colored red. Cationic residues involved in ligand binding and membrane interactions are colored blue. The hydrocarbon core boundary at the cytoplasmic side is indicated by blue dots. The layer of lipid phosphates ("P") is shown by gold dots (at 5 Å outside the hydrocarbon boundary [28]). The center of the membrane is indicated by grey dots (at 15 Å inside the boundary). All Figures were generated by PyMol

    The role of hydrophobic interactions in positioning of peripheral proteins in membranes-1

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    <p><b>Copyright information:</b></p><p>Taken from "The role of hydrophobic interactions in positioning of peripheral proteins in membranes"</p><p>http://www.biomedcentral.com/1472-6807/7/44</p><p>BMC Structural Biology 2007;7():44-44.</p><p>Published online 29 Jun 2007</p><p>PMCID:PMC1934363.</p><p></p>(A-C) or by Monte Carlo Simulations (D-F) in the hydrophobicslab. Coordinate sets of the toxins were kindly provided by Dr. Efremov [16]. The backbone of toxins is shown in ribbon model. Hydrocarbon core-penetrating residues are shown in stick model. Hydrocarbon core boundary at the extracellular side is indicated by red dots. The layer of lipid phosphates ("P") is shown by gold dots (at 5 Å outside the hydrocarbon boundary). The center of membrane is indicated by grey dots (at 15 Å inside the boundary). The orientations of each protein obtained by PPM and MC simulations are rather similar; and sets of membrane-penetrating residues are identical. However, the tilt between the protein axis and the membrane normal differ by 3° for 1rl3, by 10° for 1kxi and by 25° for 2cdx
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