Differential dynamics in the G protein-coupled receptor rhodopsin revealed by solution NMR.

Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.74). 04/2004; 101(10):3409-13. DOI: 10.1073/pnas.0308713101
Source: PubMed

ABSTRACT G protein-coupled receptors are cell-surface seven-helical membrane proteins that undergo conformational changes on activation. The mammalian photoreceptor, rhodopsin, is the best-studied member of this superfamily. Here, we provide the first evidence that activation in rhodopsin may involve differential dynamic properties of side-chain versus backbone atoms. High-resolution NMR studies of alpha-(15)N-labeled receptor revealed large backbone motions in the inactive dark state. In contrast, indole side-chain (15)N groups of tryptophans showed well resolved, equally intense NMR signals, suggesting restriction to a single specific conformation.

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    ABSTRACT: Sensory rhodopsin II (SRII) is a seven helix protein that belongs to the rhodopsin protein family. Light induced conformational changes govern SRII's function. These changes are related to the photo cycle of the protein that is comprised of various metastable states. After the completion of this cycle the protein returns to its ground state. Mutational studies of key residues will reveal the mechanism that underlies the function of the protein. The result will allow us to determine key structures at various PHs involved in the photo cycle of SRII and to understand the protein's function and mechanism.
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    ABSTRACT: Many biological membranes consist of 50% or more (by weight) membrane proteins, which constitute approximately one-third of all proteins expressed in biological organisms. Helical membrane proteins function as receptors, enzymes, and transporters, among other unique cellular roles. Additionally, most drugs have membrane proteins as their receptors, notably the superfamily of G protein-coupled receptors with seven transmembrane helices. Determining the structures of membrane proteins is a daunting task because of the effects of the membrane environment; specifically, it has been difficult to combine biologically compatible environments with the requirements for the established methods of structure determination. There is strong motivation to determine the structures in their native phospholipid bilayer environment so that perturbations from nonnatural lipids and phases do not have to be taken into account. At present, the only method that can work with proteins in liquid crystalline phospholipid bilayers is solid-state NMR spectroscopy. Expected final online publication date for the Annual Review of Analytical Chemistry Volume 6 is June 15, 2013. Please see for revised estimates.
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