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St. Petersburg Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences
Heterotrimeric GTP-binding proteins (G-proteins) are used by cells to transduce signals from the extracellular environment through surface receptors to intracellular effector proteins. One of the best model systems for studying mechanisms of G protein signaling is the rod photoreceptor visual transduction cascade. Our laboratory focuses on investigation of specific protein-protein interactions between the photoreceptor – rhodopsin, the rod G protein - transducin, and the effector enzyme - cGMPphosphodiesterase. We study the modulation of transducin by retinal regulators of G protein signaling (RGS) and other accessory proteins. To understand the activation and turn-off mechanisms of transducin and cGMP-phosphodiesterase upon transduction of a visual signal we employ tools and techniques such as transgenic mouse models, site-directed mutagenesis, synthetic peptides, site specific antibodies, cross-linking, fluorescence microscopy and spectroscopy. The high levels of sequence homology between different types of G proteins, as well as the structural similarities observed in their crystal structures suggest that numerous G protein signaling systems have similar mechanisms of activation. Our ultimate goal is to understand the mechanisms of regulation of G protein signaling at the molecular level.
1. Moussaif, M., Rubin, W.W., Kerov, V., Reh, R., Chen, D., Lem, J., Chen, C.-K., Hurley, J.B., Burns, M.E., and Artemyev, N.O. Phototransduction in a transgenic mouse model of Nougaret night blindness. J. Neurosci. 26:6863-6872, 2006. 2. Muradov, K.G., Boyd, K.K., Kerov, V., and Artemyev N.O. (2007) PDE6 in lamprey Petromyzon marinus: implications for the evolution of the visual effector in vertebrates. Biochemistry, 46:9992-10000, 2007. 3. Kerov, V., Rubin, W.W., Natochin, M., Melling, N., Burns, M.E. and Artemyev, N.O. N-terminal fatty acylation of transducin profoundly influences its localization and the kinetics of photoresponse in rods. J. Neurosci. 27:10270-10277, 2007.
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