title: Modulation of small GTPases by Legionella.
abstract: The pathogenic bacterium Legionella pneumophila interacts intimately with signaling molecules during the infection of eukaryotic host cells. Among a diverse set of regulatory molecules, host small GTPases appear to be prominent and significant targets. Small GTPases are molecular switches that regulate cellular signaling via their respective nucleotide-bound states: When bound to GDP, they are inactive, but become activated upon binding to GTP. Legionella secretes specific bacterial proteins into the cytosol of the host cell that most prominently modulate the activities of small GTPases involved in vesicular trafficking, but probably also other G-proteins. The master regulators of vesicular trafficking, i.e., Rab and Arf proteins, are majorly targeted G-proteins of Legionella proteins, and among these, Rab1 experiences the most diverse modifications. Generally, the activities of small GTPases are modulated by GDP/GTP exchange (activation), GTP hydrolysis (deactivation), membrane recruitment, post-translational modifications (phosphocholination, adenylylation), and tight and competitive binding. Here, we discuss the consequences and molecular details of the modulation of small GTPases for the infection by Legionella, with a special but not exclusive focus on Rab and Arf proteins.
authors.affiliation: Max-Planck-Institute of Molecular Physiology, Department of Physical Biochemistry, Otto-Hahn Str. 11, 44227, Dortmund, Germany, roger.goody@mpi-dortmund.mpg.de.
authors.forename: Roger S
authors.initials: RS
authors.lastname: Goody
authors.forename: Aymelt
authors.initials: A
authors.lastname: Itzen
mesh_terms: D020823:ADP-Ribosylation Factor 1 / Q000502:physiology; D006801:Humans; D007875:Legionella / Q000472:pathogenicity*; D020559:Monomeric GTP-Binding Proteins / Q000502:physiology*; D020761:rab1 GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D020823:ADP-Ribosylation Factor 1; D020559:Monomeric GTP-Binding Proteins; D020761:rab1 GTP-Binding Proteins