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Defining the Interface between the C-terminal Fragment of -Transducin and Photoactivated Rhodopsin

Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri 63110

Correspondence: Address reprint requests to Garland R. Marshall, Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, 700 S. Euclid, St. Louis, MO 63110. Tel.: 314-362-1567; Fax: 314-747-3330; Email: garland{at}pcg.wustl.edu.

A novel combination of experimental data and extensive computational modeling was used to explore probable protein-protein interactions between photoactivated rhodopsin (R*) and experimentally determined R*-bound structures of the C-terminal fragment of -transducin (Gt(340-350)) and its analogs. Rather than using one set of loop structures derived from the dark-adapted rhodopsin state, R* was modeled in this study using various energetically feasible sets of intracellular loop (IC loop) conformations proposed previously in another study. The R*-bound conformation of Gt(340-350) and several analogs were modeled using experimental transferred nuclear Overhauser effect data derived upon binding R*. Gt(340-350) and its analogs were docked to various conformations of the intracellular loops, followed by optimization of side-chain spatial positions in both R* and Gt(340-350) to obtain low-energy complexes. Finally, the structures of each complex were subjected to energy minimization using the OPLS/GBSA force field. The resulting residue-residue contacts at the interface between R* and Gt(340-350) were validated by comparison with available experimental data, primarily from mutational studies. Computational modeling performed for Gt(340-350) and its analogs when bound to R* revealed a consensus of general residue-residue interactions, necessary for efficient complex formation between R* and its Gt recognition motif.