Adenylylation of Tyr77 stabilizes Rab1b GTPase in an active state: A molecular dynamics simulation analysis

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 enzy...

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Bibliographic Details
Published in:Scientific reports 2016-01, Vol.6 (1), p.19896-19896, Article 19896
Main Authors: Luitz, Manuel P., Bomblies, Rainer, Ramcke, Evelyn, Itzen, Aymelt, Zacharias, Martin
Format: Article
Language:English
Subjects:
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Adenine
Adenosine
Adenosine Monophosphate - chemistry
Adenosine Monophosphate - metabolism
AMP
Binding sites
Conformation
Crystal structure
Electrostatic properties
Guanosine triphosphatases
Guanosine triphosphate
Guanosine Triphosphate - chemistry
Guanosine Triphosphate - metabolism
Humanities and Social Sciences
Molecular dynamics
Molecular Dynamics Simulation
multidisciplinary
Protein Binding
Protein Conformation
Protein Stability
Proteins
rab1 GTP-Binding Proteins - chemistry
rab1 GTP-Binding Proteins - metabolism
Ras protein
Science
Simulation
Simulation analysis
Static Electricity
Tyrosine - chemistry
Tyrosine - metabolism
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep19896