Conserved waters mediate structural and functional activation of family A (rhodopsin-like) G protein-coupled receptors. Export

@article{citeulike:4650832, abstract = {G protein-coupled receptors with seven transmembrane alpha-helices (GPCRs) comprise the largest receptor superfamily and are involved in detecting a wide variety of extracellular stimuli. The availability of high-resolution crystal structures of five prototypical GPCRs, bovine and squid rhodopsin, engineered A(2A)-adenosine, beta(1)- and beta(2)-adrenergic receptors, permits comparative analysis of features common to these and likely all GPCRs. We provide an analysis of the distribution of water molecules in the transmembrane region of these GPCR structures and find conserved contacts with microdomains demonstrated to be involved in receptor activation. Colocalization of water molecules associating with highly conserved and functionally important residues in several of these GPCR crystal structures supports the notion that these waters are likely to be as important to proper receptor function as the conserved residues. Moreover, in the absence of large conformational changes in rhodopsin after photoactivation, we propose that ordered waters contribute to the functional plasticity needed to transmit activation signals from the retinal-binding pocket to the cytoplasmic face of rhodopsin and that fundamental features of the mechanism of activation, involving these conserved waters, are shared by many if not all family A receptors.}, author = {Angel, Thomas E. and Chance, Mark R. and Palczewski, Krzysztof}, citeulike-article-id = {4650832}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0903545106}, citeulike-linkout-1 = {http://www.pnas.org/content/106/21/8555.abstract}, citeulike-linkout-2 = {http://www.pnas.org/content/106/21/8555.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/19433801}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=19433801}, day = {26}, doi = {10.1073/pnas.0903545106}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, keywords = {activation, gpcr, review, structure, water}, month = {May}, number = {21}, pages = {8555--8560}, posted-at = {2009-10-06 18:17:17}, priority = {2}, title = {Conserved waters mediate structural and functional activation of family A (rhodopsin-like) G protein-coupled receptors.}, url = {http://dx.doi.org/10.1073/pnas.0903545106}, volume = {106}, year = {2009} }

TY - JOUR ID - citeulike:4650832 L3 - citeulike-article-id:4650832 N2 - G protein-coupled receptors with seven transmembrane alpha-helices (GPCRs) comprise the largest receptor superfamily and are involved in detecting a wide variety of extracellular stimuli. The availability of high-resolution crystal structures of five prototypical GPCRs, bovine and squid rhodopsin, engineered A(2A)-adenosine, beta(1)- and beta(2)-adrenergic receptors, permits comparative analysis of features common to these and likely all GPCRs. We provide an analysis of the distribution of water molecules in the transmembrane region of these GPCR structures and find conserved contacts with microdomains demonstrated to be involved in receptor activation. Colocalization of water molecules associating with highly conserved and functionally important residues in several of these GPCR crystal structures supports the notion that these waters are likely to be as important to proper receptor function as the conserved residues. Moreover, in the absence of large conformational changes in rhodopsin after photoactivation, we propose that ordered waters contribute to the functional plasticity needed to transmit activation signals from the retinal-binding pocket to the cytoplasmic face of rhodopsin and that fundamental features of the mechanism of activation, involving these conserved waters, are shared by many if not all family A receptors. IS - 21 JF - Proceedings of the National Academy of Sciences of the United States of America SN - 1091-6490 EP - 8560 TI - Conserved waters mediate structural and functional activation of family A (rhodopsin-like) G protein-coupled receptors. VL - 106 SP - 8555 KW - activation KW - gpcr KW - review KW - structure KW - water AU - Angel, Thomas AU - Chance, Mark AU - Palczewski, Krzysztof PY - 2009/05/26/ UR - http://dx.doi.org/10.1073/pnas.0903545106 ER -