Structural Waters Define a Functional Channel Mediating Activation of the GPCR, rhodopsin
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 H2O18 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.
- Research Organization:
- Brookhaven National Lab. (BNL), Upton, NY (United States). National Synchrotron Light Source
- Sponsoring Organization:
- Doe - Office Of Science
- DOE Contract Number:
- DE-AC02-98CH10886
- OSTI ID:
- 980535
- Report Number(s):
- BNL-93453-2010-JA; TRN: US201015%%1920
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, Issue 34
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
99 GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE
CHAINS
COMMUNICATIONS
COUPLING
DYNAMICS
FUNCTIONALS
GROUND STATES
HYDROXYL RADICALS
INSPECTION
MEMBRANE PROTEINS
MIXING
MOLECULES
PLASTICITY
PROTEINS
RADIOLYSIS
RECEPTORS
RESIDUES
RHODOPSIN
SIGNALS
SOLVENTS
TRANSMISSION
national synchrotron light source