title: Effect of N-Terminal Myristoylation on the Active Conformation of Gαi1-GTP.
abstract: 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 Gαisubunit 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 Gαi1and 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.
authors.affiliation: Institut des Sciences et Ingénierie Chimiques, École Polytechnique Fédérale de Lausanne (EPFL) , CH-1015 Lausanne, Switzerland.
authors.forename: Siri C
authors.identifier: http://orcid.org/0000-0001-6995-8389
authors.initials: SC
authors.lastname: van Keulen
authors.affiliation: Institut des Sciences et Ingénierie Chimiques, École Polytechnique Fédérale de Lausanne (EPFL) , CH-1015 Lausanne, Switzerland.
authors.forename: Ursula
authors.initials: U
authors.lastname: Rothlisberger
mesh_terms: D020823:ADP-Ribosylation Factor 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000737:chemistry / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000737:chemistry / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000737:chemistry* / Q000378:metabolism; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D019814:Myristic Acid / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D000072417:Protein Domains; D017433:Protein Structure, Secondary; D051381:Rats; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity
chemical_list: D019814:Myristic Acid; D006153:Guanosine Diphosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D020823:ADP-Ribosylation Factor 1