Modeling Flexible Loops in the Dark-Adapted and Activated States of Rhodopsin, a Prototypical G-Protein-Coupled Receptor

• Published in: Biophysical journal Vol. 89; no. 6; pp. 3780 - 3789
• Main Authors: Nikiforovich, Gregory V., Marshall, Garland R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2005; Biophysical Society
• Subjects: Adaptation, Physiological - radiation effects; Amino acids; Biophysical Theory and Modeling; Cell Membrane - chemistry; Computer Simulation; Dark Adaptation; Light; Models, Chemical; Models, Molecular; Molecular structure; Protein Conformation - radiation effects; Protein folding; Protein Structure, Secondary - radiation effects; Proteins; Receptors, G-Protein-Coupled - chemistry; Receptors, G-Protein-Coupled - radiation effects; Rhodopsin - chemistry; Rhodopsin - radiation effects; Studies
• ISSN: 0006-3495; 1542-0086
• DOI: 10.1529/biophysj.105.070722

Conformational possibilities of flexible loops in rhodopsin, a prototypical G-protein-coupled receptor, were studied by modeling both in the dark-adapted (R) and activated (R*) states. Loop structures were built onto templates representing the R and R* states of the TM region of rhodopsin developed previously (G. V. Nikiforovich and G. R. Marshall. 2003. Biochemistry. 42:9110). Geometrical sampling and energy calculations were performed for each individual loop, as well as for the interacting intracellular loops IC1, IC2, and IC3 and the extracellular loops EC1, EC2, and EC3 mounted on the R and R* templates. Calculations revealed that the intra- and extracellular loops of rhodopsin possess low-energy structures corresponding to large conformational movements both in the R and R* states. Results of these calculations are in good agreement with the x-ray data available for the dark-adapted rhodopsin as well as with the available experimental biophysical data on the disulfide-linked mutants of rhodopsin. The calculated results are used to exemplify how the combined application of the results of independent calculations with emerging experimental data can be used to select plausible three-dimensional structures of the loops in rhodopsin.