Internal hydration increases during activation of the G-protein-coupled receptor rhodopsin

JOURNAL OF MOLECULAR BIOLOGY

卷:381

Article

Grossfield, Alan¹  Pitman, Michael C.¹  Feller, Scott E.²  Soubias, Olivier³  Gawrisch, Klaus³ 

[1] IBM Corp, Thomas J Watson Res Ctr, Yorktown Hts, NY 10598 USA

[2] Wabash Coll, Dept Chem, Crawfordsville, IN 47933 USA

[3] NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA

关键词: molecular dynamics;    NMR;    hydration;    GPCR;   

DOI  :  10.1016/j.jmb.2008.05.036

来源: Elsevier

【 摘 要 】

Rhodopsin, the membrane protein responsible for dim-light vision, until recently was the only G-protein-coupled receptor (GPCR) with a known crystal structure. As a result, there is enormous interest in studying its structure, dynamics, and function. Here we report the results of three all-atom molecular dynamics simulations, each at least 1.5 mu s, which predict that substantial changes in internal hydration play a functional role in rhodopsin activation. We confirm with H magic angle spinning NMR that the increased hydration is specific to the metarhodopsin-I intermediate. The internal water molecules interact with several conserved residues, suggesting that changes in internal hydration may be important during the activation of other GPCRs. The results serve to illustrate the synergism of long-time-scale molecular dynamics simulations and NMR in enhancing our understanding of GPCR function. (c) 2008 Published by Elsevier Ltd.

【 授权许可】

Free