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

Yoonji Lee, Songmi Kim, Sun Choi, Changbong Hyeon

Research output: Contribution to journalArticle

11 Citations (Scopus)

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 ∼O(10 2 ) ps to ∼O(10 2 ) ns. Especially, water molecules, exhibiting ultraslow relaxation (∼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.

Original languageEnglish (US)
Pages (from-to)1180-1191
Number of pages12
JournalBiophysical Journal
Volume111
Issue number6
DOIs
StatePublished - Sep 20 2016
Externally publishedYes

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Adenosine A2A Receptors
Water
G-Protein-Coupled Receptors
Molecular Dynamics Simulation

ASJC Scopus subject areas

  • Biophysics

Cite this

Ultraslow Water-Mediated Transmembrane Interactions Regulate the Activation of A 2A Adenosine Receptor . / Lee, Yoonji; Kim, Songmi; Choi, Sun; Hyeon, Changbong.

In: Biophysical Journal, Vol. 111, No. 6, 20.09.2016, p. 1180-1191.

Research output: Contribution to journalArticle

Lee, Yoonji ; Kim, Songmi ; Choi, Sun ; Hyeon, Changbong. / Ultraslow Water-Mediated Transmembrane Interactions Regulate the Activation of A 2A Adenosine Receptor In: Biophysical Journal. 2016 ; Vol. 111, No. 6. pp. 1180-1191.
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