title: The Legionella effector protein DrrA AMPylates the membrane traffic regulator Rab1b.
abstract: 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.
authors.affiliation: Department of Physical Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, NRW, 44227, Germany.
authors.forename: Matthias P
authors.initials: MP
authors.lastname: Müller
authors.forename: Heide
authors.initials: H
authors.lastname: Peters
authors.forename: Julia
authors.initials: J
authors.lastname: Blümer
authors.forename: Wulf
authors.initials: W
authors.lastname: Blankenfeldt
authors.forename: Roger S
authors.initials: RS
authors.lastname: Goody
authors.forename: Aymelt
authors.initials: A
authors.lastname: Itzen
mesh_terms: D000249:Adenosine Monophosphate / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D019556:COS Cells; D002522:Chlorocebus aethiops; D003461:Crystallography; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D016952:Legionella pneumophila / Q000502:physiology*; D013058:Mass Spectrometry; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D020761:rab1 GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D020662:Guanine Nucleotide Exchange Factors; C539733:SidM protein, Legionella pneumophila; D000249:Adenosine Monophosphate; D020691:rab GTP-Binding Proteins; D020761:rab1 GTP-Binding Proteins