Back
Full-text
Journal article

Effect of N-Terminal Myristoylation on the Active Conformation of Gαi1-GTP.

  • van Keulen SC Institut des Sciences et Ingénierie Chimiques, École Polytechnique Fédérale de Lausanne (EPFL) , CH-1015 Lausanne, Switzerland.
  • Rothlisberger U Institut des Sciences et Ingénierie Chimiques, École Polytechnique Fédérale de Lausanne (EPFL) , CH-1015 Lausanne, Switzerland.
  • 2016-12-13
Published in:
  • Biochemistry. - 2017
ADP-Ribosylation Factor 1
Amino Acid Sequence
Animals
Crystallography, X-Ray
GTP-Binding Protein alpha Subunits, Gi-Go
Guanosine 5'-O-(3-Thiotriphosphate)
Guanosine Diphosphate
Guanosine Triphosphate
Molecular Conformation
Molecular Dynamics Simulation
Myristic Acid
Protein Binding
Protein Conformation
Protein Domains
Protein Structure, Secondary
Rats
Sequence Homology, Amino Acid
Static Electricity
English 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.
Language
  • English
Open access status
green
Identifiers
Persistent URL
https://sonar.ch/global/documents/231599
Statistics
Document views: 19 File downloads:
  • Full-text: 0