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Ultraslow Water-Mediated Transmembrane Interactions Regulate the Activation of A(2A) Adenosine Receptor

Title
Ultraslow Water-Mediated Transmembrane Interactions Regulate the Activation of A(2A) Adenosine Receptor
Authors
Lee, YoonjiKim, SongmiChoi, SunHyeon, Changbong
Ewha Authors
최선이윤지
SCOPUS Author ID
최선scopus; 이윤지scopus
Issue Date
2016
Journal Title
BIOPHYSICAL JOURNAL
ISSN
0006-3495JCR Link1542-0086JCR Link
Citation
vol. 111, no. 6, pp. 1180 - 1191
Publisher
CELL PRESS
Indexed
SCI; SCIE; SCOPUS WOS
Abstract
Water molecules inside a G-protein coupled receptor (GPCR) have recently been spotlighted in a series of crystal structures. To decipher the dynamics and functional roles of internal water molecules in GPCR activity, we studied the A(2A) adenosine receptor using microsecond molecular-dynamics simulations. Our study finds that the amount of water flux across the transmembrane (TM) domain varies depending on the receptor state, and that the water molecules of the TM channel in the active state flow three times more slowly than those in the inactive state. Depending on the location in solvent-protein interface as well as the receptor state, the average residence time of water in each residue varies from similar to O(10(2)) ps to similar to O(10(2)) ns. Especially, water molecules, exhibiting ultraslow relaxation (similar to O(10(2)) ns) in the active state, are found around the microswitch residues that are considered activity hotspots for GPCR function. A continuous allosteric network spanning the TM domain, arising from water-mediated contacts, is unique in the active state, underscoring the importance of slow water molecules in the activation of GPCRs.
DOI
10.1016/j.bpj.2016.08.002
Appears in Collections:
약학대학 > 약학과 > Journal papers
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