G Protein-Coupled Receptor Rhodopsin: A Prospectus

Filipek, Sławomir; Stenkamp, Ronald E.; Teller, David C.; Palczewski, Krzysztof

doi:10.1146/annurev.physiol.65.092101.142611

Cited by 230 publications

(203 citation statements)

References 170 publications

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“…A disulfide bond between Cys-110 on TM3 and Cys-187 in E2 tethers a compact extracellular domain, the so-called "retinal plug" to the 7TM domain. The "retinal plug" includes two antiparallel β-sheets in the N-terminus (strands β1/β2) and in loop E2 (strands β3/β4), respectively [49]. E2 folds back into the protein to contribute…”

Section: Structure Of Rhodopsinmentioning

confidence: 99%

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Crystal structure of the ligand-free G-protein-coupled receptor opsin

Park

Scheerer

Hofmann

et al. 2008

Nature

858

925

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Compared with the known structure of inactive rhodopsin, opsin displays prominent structural changes in the conserved E(D)RY and NPxxY(x) 5,6 F regions and TM5-TM7. At the cytoplasmic side, TM6 is tilted outwards by 6-7 Å, whereas the helix structure of TM5 is more elongated and close to TM6. These structural changes, of which some are attributed to an active GPCR state, reorganize the empty retinal binding pocket to disclose two openings for exit and entry of retinal. The opsin structure thus sheds new light on binding of hydrophobic ligands to GPCRs, GPCR activation and signal transfer to the G protein.

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Section: Structure Of Rhodopsinmentioning

confidence: 99%

“…Also the cytoplasmic loops (C1 -C3) of opsin and rhodopsin have significantly higher temperature factors (Bfactor) than the TM segments. On the other hand, the extracellular loops and the N-terminus form a compact extracellular domain, the so-called "retinal plug" [49,113]. The "retinal plug"…”

Section: Overall Structure Of Opsinmentioning

confidence: 99%

Crystal structure of the ligand-free G-protein-coupled receptor opsin

Park

Scheerer

Hofmann

et al. 2008

Nature

858

925

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“…3,[128][129][130] This is especially important due to the large number of important pharmacological targets within the large GPCR family. [131][132][133][134][135][136][137][138][139][140][141][142] In our simulation results, the nature of the coupling between a local conformational change and a large-scale helix and loop change may be similar across the GPCR family.…”

Section: Implications For Other Gpcr Systemsmentioning

confidence: 99%

“…[1][2][3][4][5][6] ). It is also the first GPCR with a measured tertiary structure 7 and is thus an excellent candidate for yielding insight into the molecular details of GPCR function.…”

Section: Introductionmentioning

confidence: 99%

How a small change in retinal leads to G‐protein activation: Initial events suggested by molecular dynamics calculations

Stevens

Woolf

2006

Proteins

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Rhodopsin is the prototypical G-protein coupled receptor, coupling light activation with high efficiency to signaling molecules. The dark-state X-ray structures of the protein provide a starting point for consideration of the relaxation from initial light activation to conformational changes that may lead to signaling. In this study we create an energetically unstable retinal in the light activated state and then use molecular dynamics simulations to examine the types of compensation, relaxation, and conformational changes that occur following the cis-trans light activation. The results suggest that changes occur throughout the protein, with changes in the orientation of Helices 5 and 6, a closer interaction between Ala 169 on Helix 4 and retinal, and a shift in the Schiff base counterion that also reflects changes in sidechain interactions with the retinal. Taken together, the simulation is suggestive of the types of changes that lead from local conformational change to light-activated signaling in this prototypical system.

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“…2,3 The disks, with dimensions of about 1 m diam, 4,5 are regularly stacked on top of each other with a repeat distance of 300 Å. 4 The visual pigment rhodopsin ͑Rh͒, an integral membrane protein, accounts for about 90% 6 of total disk protein content. Photoreceptor disks are continuously renewed through formation of new disks at the base of the outer segment, displaced distally along the length of the outer segment, and eventual detachment and phagocytosis occurs by adjacent pigment epithelial cells.…”

mentioning

confidence: 99%

Confocal laser scanning microscopy of retinal rod outer segment intact disks: new labeling technique

et al. 2007

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Abstract. Vertebrate retinal rod outer segment disks house the proteins involved in the phototransduction cascade that converts light into neuronal signal. We develop a technique for the immunofluorescent labeling of osmotically intact isolated rod outer segment disks for confocal laser scanning microscopy imaging. Osmotically intact Ficoll-flotation isolated bovine disks are directly labeled with antibodies in solution. For the first time, osmotically intact single disks can be visualized. Thus, imaging of purified disks, based on advanced optical techniques, may serve as a powerful complement to other methods in studies on phototransduction. In fact, even though much is known about the rod outer segment photoresponse, some unanswered questions remain, particularly about ATP supply, light adaptation, and morphogenesis. Oct. 3, 2007. Confocal laser scanning microscopy ͑CLSM͒ is a valuable tool for obtaining high-resolution images and 3-D reconstructions. 1 Vertebrate rod photoreceptors, the neurons responsible for visual phototransduction, mediate vision at low-light intensities using a modified cilium ͑called the outer segment͒ for the detection of light. The rod outer segment ͑rod OS͒ is packed with hundreds of membrane sacs, called disks, on the surface of which the initial biochemical reactions of visual transduction take place. 2,3 The disks, with dimensions of about 1 m diam, 4,5 are regularly stacked on top of each other with a repeat distance of 300 Å. 4 The visual pigment rhodopsin ͑Rh͒, an integral membrane protein, accounts for about 90% 6 of total disk protein content. Photoreceptor disks are continuously renewed through formation of new disks at the base of the outer segment, displaced distally along the length of the outer segment, and eventual detachment and phagocytosis occurs by adjacent pigment epithelial cells. 7 Several microscopy techniques have been used to analyze the morphological organization of rods and to identify the membrane proteins in rod OS. For example, measurements of the ellipsoid mitochondria density, sizes, and shapes of inner segments were conducted by electron microscopy and Nomads differential interference contrast ͑NDIC͒ imaging. 8 Studies on the stability of Rh in native membranes were done by single-molecule force spectroscopy. 9 Moreover, a recent progress in modeling the native conformation of Rh was based on topography of the disk membranes recorded by an atomic force microscope ͑AFM͒. 9 CLSM was only used on whole retina or rod OS to observe the protein distribution in the disk incisures. 10 Therefore, even though rod imaging has been achieved in many ways, to the best of our knowledge, until now no study has been reported regarding the application of immunofluorescence for confocal optical imaging of isolated intact disks. In fact, even though fluorescent optical imaging is among the most widely used approach for studying cells in vivo, it is not easily applicable for subcellular fractions. Apart from the classic inclusion methods, it is difficult to isolate an...

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G Protein-Coupled Receptor Rhodopsin: A Prospectus

Cited by 230 publications

References 170 publications

Crystal structure of the ligand-free G-protein-coupled receptor opsin

Crystal structure of the ligand-free G-protein-coupled receptor opsin

How a small change in retinal leads to G‐protein activation: Initial events suggested by molecular dynamics calculations

Confocal laser scanning microscopy of retinal rod outer segment intact disks: new labeling technique

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