The Active Conformation Of Opsin (ops∗): Role In Signal Transduction And Regeneration

Abstract

Functional modules are specific subsets of the proteome, which fulfil an autonomous function in living cells. Functional modules in retinal photoreceptors include those devoted to phototransduction and regeneration [1]. In signal transduction, rhodopsin is kept inactive in the dark by a set of structural elements and residues conserved in the E(D)RY and NPxxY(x)5,6F regions of the receptor protein. On light activation, the same residues are crucial determinants of the Meta II state [2], with the hallmark of a motion of the sixth of the seven transmembrane helices [3]. The same elements stabilize the ligand free active form of the opsin apoprotein, Ops∗ [4], and build up new interactions of Ops∗ with the G-protein α-subunit C-terminal interaction site [5]. The Ops∗ state can thus act as the key element in both functional modules of the rod cell. In signal transduction, the Ops∗ conformation is present in the highly active Meta II photoproduct. In rhodopsin regeneration, Ops∗ facilitates the uptake of 11-cis-retinal into the binding site [6] and causes the visual system to behave as if it is experiencing an “equivalent background” [7]. 1. Hofmann, K.P., et al., Trends Biochem Sci, 2006. 31, 497. 2. Knierim, B., et al., PNAS 2007 104, 4967. 3. Altenbach, C., et al., PNAS 2008. 105, 7439. 4. Park, J.H., et al., Nature, 2008. 454, 183. 5. Scheerer, P., et al., Nature, 2008. 455, 497. 6. Kefalov, V.J., et al., Neuron, 2001, 29, 749. 7. Lamb, T.D. & E.N. Pugh, Jr.,Prog Retin Eye Res, 2004. 23, 307.