Myristoylation exerts direct and allosteric effects on Gα conformation and dynamics in solution.

Biochemistry
Anita M PreiningerH E Hamm

Abstract

Coupling of heterotrimeric G proteins to activated G protein-coupled receptors results in nucleotide exchange on the Gα subunit, which in turn decreases its affinity for both Gβγ and activated receptors. N-Terminal myristoylation of Gα subunits aids in membrane localization of inactive G proteins. Despite the presence of the covalently attached myristoyl group, Gα proteins are highly soluble after GTP binding. This study investigated factors facilitating the solubility of the activated, myristoylated protein. In doing so, we also identified myristoylation-dependent differences in regions of Gα known to play important roles in interactions with receptors, effectors, and nucleotide binding. Amide hydrogen-deuterium exchange and site-directed fluorescence of activated proteins revealed a solvent-protected amino terminus that was enhanced by myristoylation. Furthermore, fluorescence quenching confirmed that the myristoylated amino terminus is in proximity to the Switch II region in the activated protein. Myristoylation also stabilized the interaction between the guanine ring and the base of the α5 helix that contacts the bound nucleotide. The allosteric effects of myristoylation on protein structure, function, and localization indi...Continue Reading

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Citations

Dec 3, 2013·Nature Structural & Molecular Biology·Nathan S AlexanderJens Meiler
Apr 23, 2013·Journal of Molecular Biology·Anita M PreiningerHeidi E Hamm
Mar 8, 2013·Journal of Structural Biology·Heidi E HammAnita M Preininger
Apr 9, 2013·Progress in Retinal and Eye Research·Jillian N PearringVadim Y Arshavsky
Apr 28, 2018·Physiological Genomics·Katherine J PerschbacherJustin L Grobe
Jul 28, 2016·The Journal of Biological Chemistry·Ali I KayaHeidi E Hamm
Sep 12, 2017·PLoS Computational Biology·Siri Camee van Keulen, Ursula Rothlisberger
Dec 13, 2016·Biochemistry·Siri C van Keulen, Ursula Rothlisberger

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