Structural waters define a functional channel mediating activation of the GPCR, rhodopsin. Export

@article{citeulike:5663255, abstract = {Structural water molecules may act as prosthetic groups indispensable for proper protein function. In the case of allosteric activation of G protein-coupled receptors (GPCRs), water likely imparts structural plasticity required for agonist-induced signal transmission. Inspection of structures of GPCR superfamily members reveals the presence of conserved embedded water molecules likely important to GPCR function. Coupling radiolytic hydroxyl radical labeling with rapid H(2)O(18) solvent mixing, we observed no exchange of these structural waters with bulk solvent in either ground state or for the Meta II or opsin states. However, the radiolysis approach permitted labeling of selected side chain residues within the transmembrane helices and revealed activation-induced changes in local structural constraints likely mediated by dynamics of both water and protein. These results suggest both a possible general mechanism for water-dependent communication in family A GPCRs based on structural conservation, and a strategy for probing membrane protein structure.}, author = {Angel, Thomas E. and Gupta, Sayan and Jastrzebska, Beata and Palczewski, Krzysztof and Chance, Mark R.}, citeulike-article-id = {5663255}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0901074106}, citeulike-linkout-1 = {http://www.pnas.org/content/106/34/14367.abstract}, citeulike-linkout-2 = {http://www.pnas.org/content/106/34/14367.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/19706523}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=19706523}, day = {25}, doi = {10.1073/pnas.0901074106}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, keywords = {activation, d250, gpcrs, n749, plasticity, rhodopsin, water}, month = {August}, number = {34}, pages = {14367--14372}, posted-at = {2009-08-28 12:52:50}, priority = {2}, title = {Structural waters define a functional channel mediating activation of the GPCR, rhodopsin.}, url = {http://dx.doi.org/10.1073/pnas.0901074106}, volume = {106}, year = {2009} }

TY - JOUR ID - citeulike:5663255 L3 - citeulike-article-id:5663255 N2 - Structural water molecules may act as prosthetic groups indispensable for proper protein function. In the case of allosteric activation of G protein-coupled receptors (GPCRs), water likely imparts structural plasticity required for agonist-induced signal transmission. Inspection of structures of GPCR superfamily members reveals the presence of conserved embedded water molecules likely important to GPCR function. Coupling radiolytic hydroxyl radical labeling with rapid H(2)O(18) solvent mixing, we observed no exchange of these structural waters with bulk solvent in either ground state or for the Meta II or opsin states. However, the radiolysis approach permitted labeling of selected side chain residues within the transmembrane helices and revealed activation-induced changes in local structural constraints likely mediated by dynamics of both water and protein. These results suggest both a possible general mechanism for water-dependent communication in family A GPCRs based on structural conservation, and a strategy for probing membrane protein structure. IS - 34 JF - Proceedings of the National Academy of Sciences of the United States of America SN - 1091-6490 EP - 14372 TI - Structural waters define a functional channel mediating activation of the GPCR, rhodopsin. VL - 106 SP - 14367 KW - activation KW - d250 KW - gpcrs KW - n749 KW - plasticity KW - rhodopsin KW - water AU - Angel, Thomas AU - Gupta, Sayan AU - Jastrzebska, Beata AU - Palczewski, Krzysztof AU - Chance, Mark PY - 2009/08/25/ UR - http://dx.doi.org/10.1073/pnas.0901074106 ER -