Legionella Effector Protein DrrA AMPylates the Membrane Traffic Regulator Rab1b

• Published in: Science (American Association for the Advancement of Science) Vol. 329; no. 5994; pp. 946 - 949
• Main Authors: Müller, Matthias P, Peters, Heide, Blümer, Julia, Blankenfeldt, Wulf, Goody, Roger S, Itzen, Aymelt
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 20.08.2010
• Subjects: Adenosine Monophosphate - metabolism; Amino acids; Animals; Bacterial Proteins - chemistry; Bacterial Proteins - metabolism; Bacterial Proteins - toxicity; Bacteriology; Biological and medical sciences; Cells; Cercopithecus aethiops; Chloroplasts; Circles; COS Cells; Crystallography; Cytotoxicity; Elution; Fundamental and applied biological sciences. Psychology; Gels; Genomes; Guanine Nucleotide Exchange Factors - chemistry; Guanine Nucleotide Exchange Factors - metabolism; Guanine Nucleotide Exchange Factors - toxicity; Legionella pneumophila; Legionella pneumophila - physiology; Mass Spectrometry; Microbiology; Models, Molecular; Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains; Protein Structure, Tertiary; Proteins; rab GTP-Binding Proteins - metabolism; rab1 GTP-Binding Proteins - metabolism; Legionellaceae; AMP; Enzyme; Triphosphoric monoester hydrolases; dGTPase; Bacteria; Hydrolases; Legionella pneumophila; Host agent relation; Esterases; Activation
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1192276

In the course of Legionnaires' disease, the bacterium Legionella pneumophila affects the intracellular vesicular trafficking of infected eukaryotic cells by recruiting the small guanosine triphosphatase (GTPase) Rab1 to the cytosolic face of the Legionella-containing vacuole. In order to accomplish this, the Legionella protein DrrA contains a specific guanine nucleotide exchange activity for Rab1 activation that exchanges guanosine triphosphate (GTP) for guanosine diphosphate on Rab1. We found that the amino-terminal domain of DrrA possesses adenosine monophosphorylation (AMPylation) activity toward the switch II region of Rab1b, leading to posttranslational covalent modification of tyrosine 77. AMPylation of switch II by DrrA restricts the access of GTPase activating proteins, thereby rendering Rab1b constitutively active.