Purchase this article with an account.
R. M. Harris, A. Hanneken, A. J. Olson; Covalent Docking of All-Trans Retinal to Rhodopsin Predicts Binding Interactions of the Metarhodopsin II and Metarhodopsin III States. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1892.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Crystal structures of rhodopsin not been generated for many of the photoactive intermediates, including the all-trans retinal bound state of Metarhodopsin II (M2) and the inactive, storage form of Metarhodopsin III (M3). We constructed computational models of both the active and inactive conformations to predict the binding interactions of all-trans retinal within the retinal binding pocket.
Using new features in AutoDock 4.0 modeling software (Morris et al. J Comp Chem 2009), all-trans retinal was covalently attached to lysine 296 and docked as a flexible residue within the retinal binding pocket of both the active and inactive conformations of opsin to predict the structure of M2. All-trans-15-syn-retinal was covalently docked in a similar manner to predict the structure of M3.
A 5 kcal/mol difference in the docking energy of all-trans retinal favored the docking to the active conformation over docking to the inactive conformation. The model places the beta-ionone head of all-trans retinal next to methionine 207 on trans-helix membrane 5 (TM5), which breaks contact with tryptophan 265 and is consistent with NMR results of Ahuja et al. (JBC 2009). The all-trans-15-syn-retinal model of the M3 state showed that the twist in the Schiff base causes the ligand to reform the salt bridge with glutamate 113 and make contact with tryptophan 265 similar to the 11-cis-retinal binding which inactivates rhodopsin.
The energy difference between the docking of covalently attached all-trans retinal to the active and inactive conformations of opsin suggest a ratchet mechanism which shifts the equilibrium towards the activated M2 state after 11-cis retinal is converted to all-trans. Conversion of all-trans retinal to all-trans-15-syn-retinal (which occurs when a photon of blue light is absorbed) causes rhodopsin to switch to the inactive M3 retinal storage state. The docking in the M3 state has similarities to the 11-cis binding, which explains the shift in equilibrium towards the inactive conformation.
This PDF is available to Subscribers Only