Mechanisms of Inter- and Intramolecular Communication in GPCRs and G Proteins Export

@article{citeulike:2522664, abstract = {Abstract: This study represents the first attempt to couple, by computational experiments, the mechanisms of intramolecular and intermolecular communication concerning a guanidine nucleotide exchange factor (GEF), the thromboxane A2 receptor (TXA2R), and the cognate G protein (Gq) in its heterotrimeric GDP-bound state. Two-way pathways mediate the communication between the receptor-G protein interface and both the agonist binding site of the receptor and the nucleotide binding site of the G protein. The increase in solvent accessibility in the neighborhoods of the highly conserved E/DRY receptor motif, in response to agonist binding, is instrumental in favoring the penetration of the C-terminus of Gq in between the cytosolic ends of H3, H5, and H6. The arginine of the E/DRY motif is predicted to be an important mediator of the intramolecular and intermolecular communication involving the TXA2R. The receptor-G protein interface is predicted to involve multiple regions from the receptor and the G protein -subunit. However, receptor contacts with the C-terminus of the 5-helix seem to be the major players in the receptor-catalyzed motion of the -helical domain with respect to the Ras-like domain and in the formation of a nucleotide exit route in between the F-helix and 6/5 loop of Gq. The inferences from this study are of wide interest, as they are expected to apply to the whole rhodopsin family, given also the considerable G protein promiscuity.}, address = {Dulbecco Telethon Institute (DTI), and Department of Chemistry, University of Modena and Reggio Emilia, via Campi 183, 41100 Modena, Italy}, author = {Raimondi, F. and Seeber, M. and Debenedetti, P. G. and Fanelli, F.}, citeulike-article-id = {2522664}, citeulike-linkout-0 = {http://dx.doi.org/10.1021/ja077268b}, citeulike-linkout-1 = {http://pubs.acs.org/doi/abs/10.1021/ja077268b}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/18335928}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=18335928}, day = {12}, doi = {10.1021/ja077268b}, journal = {J. Am. Chem. Soc.}, keywords = {activation, docking, gpcr, gproteins}, month = {March}, posted-at = {2008-05-03 17:09:50}, priority = {2}, title = {Mechanisms of Inter- and Intramolecular Communication in GPCRs and G Proteins}, url = {http://dx.doi.org/10.1021/ja077268b}, year = {2008} }

TY - JOUR ID - citeulike:2522664 L3 - citeulike-article-id:2522664 N2 - Abstract: This study represents the first attempt to couple, by computational experiments, the mechanisms of intramolecular and intermolecular communication concerning a guanidine nucleotide exchange factor (GEF), the thromboxane A2 receptor (TXA2R), and the cognate G protein (Gq) in its heterotrimeric GDP-bound state. Two-way pathways mediate the communication between the receptor-G protein interface and both the agonist binding site of the receptor and the nucleotide binding site of the G protein. The increase in solvent accessibility in the neighborhoods of the highly conserved E/DRY receptor motif, in response to agonist binding, is instrumental in favoring the penetration of the C-terminus of Gq in between the cytosolic ends of H3, H5, and H6. The arginine of the E/DRY motif is predicted to be an important mediator of the intramolecular and intermolecular communication involving the TXA2R. The receptor-G protein interface is predicted to involve multiple regions from the receptor and the G protein -subunit. However, receptor contacts with the C-terminus of the 5-helix seem to be the major players in the receptor-catalyzed motion of the -helical domain with respect to the Ras-like domain and in the formation of a nucleotide exit route in between the F-helix and 6/5 loop of Gq. The inferences from this study are of wide interest, as they are expected to apply to the whole rhodopsin family, given also the considerable G protein promiscuity. JF - J. Am. Chem. Soc. AD - Dulbecco Telethon Institute (DTI), and Department of Chemistry, University of Modena and Reggio Emilia, via Campi 183, 41100 Modena, Italy TI - Mechanisms of Inter- and Intramolecular Communication in GPCRs and G Proteins KW - activation KW - docking KW - gpcr KW - gproteins AU - Raimondi, F AU - Seeber, M AU - Debenedetti, PG AU - Fanelli, F PY - 2008/03/12/ UR - http://dx.doi.org/10.1021/ja077268b ER -