Conserved waters mediate structural and functional activation of family A (rhodopsin-like) G protein-coupled receptors
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 A2A-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.
- Research Organization:
- Brookhaven National Laboratory (BNL) National Synchrotron Light Source
- Sponsoring Organization:
- Doe - Office Of Science
- DOE Contract Number:
- AC02-98CH10886
- OSTI ID:
- 980080
- Report Number(s):
- BNL--92998-2010-JA
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 21 Vol. 106
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
99 GENERAL AND MISCELLANEOUS
AVAILABILITY
CATTLE
CONFORMATIONAL CHANGES
CRYSTAL STRUCTURE
DISTRIBUTION
FACE
FUNCTIONALS
FUNCTIONS
LICENSES
MOLECULES
PLASTICITY
RECEPTORS
RESIDUES
RHODOPSIN
SIGNALS
STIMULI
SUPPORTS
WATER
national synchrotron light source