Van Keulen, Siri C.Rothlisberger, Ursula2017-01-122017-01-122017-01-12201710.1021/acs.biochem.6b00388https://infoscience.epfl.ch/handle/20.500.14299/132865WOS:000391898400027G proteins are part of the G-protein-coupled receptor (GPCR) signal transduction cascade in which they transfer a signal from the membrane-embedded GPCR to other proteins in the cell. In the case of the inhibitory G-protein heterotrimer, permanent N-terminal myristoylation can transiently localize the G alpha(i) subunit at the membrane as well as crucially influence G alpha(i)'s function in the GTP-bound conformation. The attachment of lipids to proteins is known to be essential for membrane trafficking; however, our results suggest that lipidation is also important for protein-protein interactions during signal transduction. Here we investigate the effect of myristoylation on the structure and dynamics of soluble G alpha(i) and its possible implication for signal transduction. A 2 mu s classical molecular dynamics simulation of a myristoylated G alpha(i1)-GTP complex suggests that the myristoyl-induced conformational changes of the switch II and alpha helical domains create new possibilities for protein-protein interactions and emphasize the importance of permanent lipid attachment for the conformation proteins. and functional tunability of signaling proteins.text::journal::journal article::research article