title: De-AMPylation unmasked: modulation of host membrane trafficking.
abstract: AMPylation, a posttranslational modification in which adenosine monophosphate (AMP) is added to hydroxyl side chains of protein substrates, is employed by many bacterial pathogens to subvert host signaling pathways during infection. The Legionella pneumophila effector protein SidM is a multifunctional enzyme that targets the guanosine triphosphatase (GTPase) Rab1 to manipulate intracellular vesicular trafficking in the host cell. SidM recruits Rab1 to the membranes of Legionella-containing vacuoles and activates Rab1 through its guanine nucleotide exchange factor activity. SidM then AMPylates Rab1, converting it into a constitutively active form that cannot be accessed by LepB, a GTPase-activating protein that is secreted by L. pneumophila. However, the molecular event that eventually leads to Rab1 inactivation and subsequent removal from Legionella-containing vacuoles has remained unknown. New evidence has identified SidD as a de-AMPylase that removes AMP from Rab1, which enables its inactivation by LepB later during the infection process. This finding demonstrates a complete pathway of reversible modifications regulated by specific bacterial enzymes to modulate host membrane trafficking.
authors: Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors: Hyeilin
authors: H
authors: Ham
authors: Kim
authors: K
authors: Orth
mesh_terms: D000249:Adenosine Monophosphate / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D054884:Host-Pathogen Interactions / Q000502:physiology*; D016952:Legionella pneumophila / Q000201:enzymology*; D021381:Protein Transport / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D020761:rab1 GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D020662:Guanine Nucleotide Exchange Factors; C482639:LepB protein, Legionella pneumophila; C559758:SidD protein, Legionella pneumophila; C539733:SidM protein, Legionella pneumophila; D000249:Adenosine Monophosphate; D020761:rab1 GTP-Binding Proteins