title: Role of bulk water in hydrolysis of the rhodopsin chromophore.
abstract: Rhodopsin (Rho) is a prototypical G protein-coupled receptor that changes from an inactive conformational state to a G protein-activating state as a consequence of its retinal chromophore isomerization, 11-cis-retinal → all-trans-retinal. The photoisomerized chromophore covalently linked to Lys(296) by a Schiff base is subsequently hydrolyzed, but little is known about this reaction. Recent research indicates a significant role for tightly bound transmembrane water molecules in the Rho activation process. Atomic structures of Rho and hydroxyl radical footprinting reveal ordered waters within Rho transmembrane helices that are located close to highly conserved and functionally important receptor residues, forming a hydrogen bond network. Using (18)O-labeled H(2)O, we now report that water from bulk solvent, but not tightly bound water, is involved in the hydrolytic release of chromophore upon Rho activation by light. Moreover, small molecules (and presumably, water) enter the Rho structure from the cytoplasmic side of the membrane. Thus, this work indicates two distinct origins of water vital for Rho function.
authors: Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106-4965, USA.
authors: Beata
authors: B
authors: Jastrzebska
authors: Krzysztof
authors: K
authors: Palczewski
authors: Marcin
authors: M
authors: Golczak
mesh_terms: D000818:Animals; D002417:Cattle; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D003593:Cytoplasm / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006868:Hydrolysis; D017665:Hydroxyl Radical / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008956:Models, Chemical; D012172:Retinaldehyde / Q000737:chemistry* / Q000378:metabolism; D012243:Rhodopsin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013237:Stereoisomerism; D014867:Water / Q000737:chemistry* / Q000378:metabolism
chemical_list: D014867:Water; D017665:Hydroxyl Radical; D012243:Rhodopsin; D012172:Retinaldehyde