Exploring allosteric coupling in the α-subunit of Heterotrimeric G proteins using evolutionary and ensemble-based approaches |
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Authors: | Kemal Sayar Özlem Uğur Tong Liu Vincent J Hilser Ongun Onaran |
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Institution: | (1) Department of Pharmacology and Clinical Pharmacology, Ankara University Faculty of Medicine, Sıhhiye, 06100 Ankara, Turkey;(2) Ankara University Faculty of Medicine, and Molecular Biology and Technology Research and Development Unit, Sıhhiye, 06100 Ankara, Turkey;(3) Department of Biochemistry and Molecular Biology, and Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX 77555-1068, USA |
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Abstract: | Background Allosteric coupling, which can be defined as propagation of a perturbation at one region of the protein molecule (such as
ligand binding) to distant sites in the same molecule, constitutes the most general mechanism of regulation of protein function.
However, unlike molecular details of ligand binding, structural elements involved in allosteric effects are difficult to diagnose.
Here, we identified allosteric linkages in the α-subunits of heterotrimeric G proteins, which were evolved to transmit membrane
receptor signals by allosteric mechanisms, by using two different approaches that utilize fundamentally different and independent
information. |
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