title: De-AMPylation of the small GTPase Rab1 by the pathogen Legionella pneumophila.
abstract: The bacterial pathogen Legionella pneumophila exploits host cell vesicle transport by transiently manipulating the activity of the small guanosine triphosphatase (GTPase) Rab1. The effector protein SidM recruits Rab1 to the Legionella-containing vacuole (LCV), where it activates Rab1 and then AMPylates it by covalently adding adenosine monophosphate (AMP). L. pneumophila GTPase-activating protein LepB inactivates Rab1 before its removal from LCVs. Because LepB cannot bind AMPylated Rab1, the molecular events leading to Rab1 inactivation are unknown. We found that the effector protein SidD from L. pneumophila catalyzed AMP release from Rab1, generating de-AMPylated Rab1 accessible for inactivation by LepB. L. pneumophila mutants lacking SidD were defective for Rab1 removal from LCVs, identifying SidD as the missing link connecting the processes of early Rab1 accumulation and subsequent Rab1 removal during infection.
authors.affiliation: Cell Biology and Metabolism Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: M Ramona
authors.initials: MR
authors.lastname: Neunuebel
authors.forename: Yang
authors.initials: Y
authors.lastname: Chen
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Gaspar
authors.forename: Peter S
authors.initials: PS
authors.lastname: Backlund
authors.forename: Alfred
authors.initials: A
authors.lastname: Yergey
authors.forename: Matthias P
authors.initials: MP
authors.lastname: Machner
mesh_terms: D000249:Adenosine Monophosphate / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D019556:COS Cells; D002522:Chlorocebus aethiops; D006056:Golgi Apparatus / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006157:Guanosine Monophosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D016952:Legionella pneumophila / Q000378:metabolism* / Q000472:pathogenicity; D008024:Ligands; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008805:Mice, Inbred A; D008954:Models, Biological; D050505:Mutant Proteins / Q000378:metabolism; D020298:U937 Cells; D014617:Vacuoles / Q000378:metabolism / Q000382:microbiology*; D020761:rab1 GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D020662:Guanine Nucleotide Exchange Factors; C482639:LepB protein, Legionella pneumophila; D008024:Ligands; D050505:Mutant Proteins; C559758:SidD protein, Legionella pneumophila; C539733:SidM protein, Legionella pneumophila; D000249:Adenosine Monophosphate; D006157:Guanosine Monophosphate; D006160:Guanosine Triphosphate; D020761:rab1 GTP-Binding Proteins