Effect of N-Terminal Myristoylation on the Active Conformation of Gαi1–GTP
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- 作者：Siri C. van KeulenUrsula Rothlisberger
- 刊名：Biochemistry
- 出版年：2017
- 出版时间：January 10, 2017
- 年：2017
- 卷：56
- 期：1
- 页码：271-280
- 全文大小：778K
- ISSN：1520-4995
文摘
G 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 Gαi subunit at the membrane as well as crucially influence Gαi’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 Gαi1 and its possible implication for signal transduction. A 2 μs classical molecular dynamics simulation of a myristoylated Gαi1–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 and functional tunability of signaling proteins.