title: Adenylylation of Tyr77 stabilizes Rab1b GTPase in an active state: A molecular dynamics simulation analysis.
abstract: The pathogenic pathway of Legionella pneumophila exploits the intercellular vesicle transport system via the posttranslational attachment of adenosine monophosphate (AMP) to the Tyr77 sidechain of human Ras like GTPase Rab1b. The modification, termed adenylylation, is performed by the bacterial enzyme DrrA/SidM, however the effect on conformational properties of the molecular switch mechanism of Rab1b remained unresolved. In this study we find that the adenylylation of Tyr77 stabilizes the active Rab1b state by locking the switch in the active signaling conformation independent of bound GTP or GDP and that electrostatic interactions due to the additional negative charge in the switch region make significant contributions. The stacking interaction between adenine and Phe45 however, seems to have only minor influence on this stabilisation. The results may also have implications for the mechanistic understanding of conformational switching in other signaling proteins.
authors.affiliation: Physics Department T38, Technische Universität München, 85748 Garching, Germany.
authors.forename: Manuel P
authors.initials: MP
authors.lastname: Luitz
authors.affiliation: Physics Department T38, Technische Universität München, 85748 Garching, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Bomblies
authors.affiliation: Center for Integrated Protein Science Munich, Technische Universität München, Department Chemistry, 85748 Garching, Germany.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Ramcke
authors.affiliation: Center for Integrated Protein Science Munich, Technische Universität München, Department Chemistry, 85748 Garching, Germany.
authors.forename: Aymelt
authors.initials: A
authors.lastname: Itzen
authors.affiliation: Physics Department T38, Technische Universität München, 85748 Garching, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Zacharias
mesh_terms: D000249:Adenosine Monophosphate / Q000737:chemistry / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011487:Protein Conformation; D055550:Protein Stability; D055672:Static Electricity; D014443:Tyrosine / Q000737:chemistry* / Q000378:metabolism; D020761:rab1 GTP-Binding Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000249:Adenosine Monophosphate; D014443:Tyrosine; D006160:Guanosine Triphosphate; D020761:rab1 GTP-Binding Proteins
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