The Role of Electrostatic Interactions in the Regulation of the Membrane Association of G Protein beta gamma Heterodimers Export

@article{murray:01, abstract = {In this paper we report calculations of electrostatic interactions between the transducin (Gt) [beta][gamma] heterodimer (Gt[beta][gamma]) and phospholipid membranes. Although membrane association of Gt[beta][gamma] is due primarily to the hydrophobic penetration into the membrane interior of a farnesyl chain attached to the [gamma] subunit, structural studies have revealed that there is a prominent patch of basic residues on the surface of the [beta] subunit surrounding the site of farnesylation that is exposed upon dissociation from the Gt[alpha] subunit. Moreover, phosducin, which produces dissociation of Gt[beta][gamma] from membranes, interacts directly with Gt[beta][gamma] and introduces a cluster of acidic residues into this region. The calculations, which are based on the finite difference Poisson-Boltzmann method, account for a number of experimental observations and suggest that charged residues play a role in mediating protein-membrane interactions. Specifically, the calculations predict the following. 1) Favorable electrostatic interactions enhance the membrane partitioning due to the farnesyl group by an order of magnitude although Gt[beta][gamma] has a large net negative charge ([-]12). 2) This electrostatic attraction positions Gt[beta][gamma] so that residues implicated in mediating the interaction of Gt[beta][gamma] with its membrane-bound effectors are close to the membrane surface. 3) The binding of phosducin to Gt[beta][gamma] diminishes the membrane partitioning of Gt[beta][gamma] by an order of magnitude. 4) Lowering the ionic strength of the solution converts the electrostatic attraction into a repulsion. Sequence analysis and homology model building suggest that our conclusions may be generalized to other G[beta][gamma] and phosducin isoforms as well. 10.1074/jbc.M101784200}, author = {Murray, Diana and Mclaughlin, Stuart and Honig, Barry}, citeulike-article-id = {3862873}, citeulike-linkout-0 = {http://dx.doi.org/10.1074/jbc.M101784200}, citeulike-linkout-1 = {http://www.jbc.org/cgi/content/abstract/276/48/45153}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/11557749}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=11557749}, day = {21}, doi = {10.1074/jbc.M101784200}, journal = {J. Biol. Chem.}, keywords = {electrostatics, g-protein, membrane-association}, month = {November}, number = {48}, pages = {45153--45159}, posted-at = {2009-01-08 19:49:36}, priority = {0}, title = {The Role of Electrostatic Interactions in the Regulation of the Membrane Association of G Protein beta gamma Heterodimers}, url = {http://dx.doi.org/10.1074/jbc.M101784200}, volume = {276}, year = {2001} }

TY - JOUR ID - murray:01 L3 - citeulike-article-id:3862873 N2 - In this paper we report calculations of electrostatic interactions between the transducin (Gt) [beta][gamma] heterodimer (Gt[beta][gamma]) and phospholipid membranes. Although membrane association of Gt[beta][gamma] is due primarily to the hydrophobic penetration into the membrane interior of a farnesyl chain attached to the [gamma] subunit, structural studies have revealed that there is a prominent patch of basic residues on the surface of the [beta] subunit surrounding the site of farnesylation that is exposed upon dissociation from the Gt[alpha] subunit. Moreover, phosducin, which produces dissociation of Gt[beta][gamma] from membranes, interacts directly with Gt[beta][gamma] and introduces a cluster of acidic residues into this region. The calculations, which are based on the finite difference Poisson-Boltzmann method, account for a number of experimental observations and suggest that charged residues play a role in mediating protein-membrane interactions. Specifically, the calculations predict the following. 1) Favorable electrostatic interactions enhance the membrane partitioning due to the farnesyl group by an order of magnitude although Gt[beta][gamma] has a large net negative charge ([-]12). 2) This electrostatic attraction positions Gt[beta][gamma] so that residues implicated in mediating the interaction of Gt[beta][gamma] with its membrane-bound effectors are close to the membrane surface. 3) The binding of phosducin to Gt[beta][gamma] diminishes the membrane partitioning of Gt[beta][gamma] by an order of magnitude. 4) Lowering the ionic strength of the solution converts the electrostatic attraction into a repulsion. Sequence analysis and homology model building suggest that our conclusions may be generalized to other G[beta][gamma] and phosducin isoforms as well. 10.1074/jbc.M101784200 IS - 48 JF - J. Biol. Chem. EP - 45159 TI - The Role of Electrostatic Interactions in the Regulation of the Membrane Association of G Protein beta gamma Heterodimers VL - 276 SP - 45153 KW - electrostatics KW - g-protein KW - membrane-association AU - Murray, Diana AU - Mclaughlin, Stuart AU - Honig, Barry PY - 2001/11/21/ UR - http://dx.doi.org/10.1074/jbc.M101784200 ER -