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Science 329 (5994): 946-949

Copyright © 2010 by the American Association for the Advancement of Science

The Legionella Effector Protein DrrA AMPylates the Membrane Traffic Regulator Rab1b

Matthias P. Müller,* Heide Peters,* Julia Blümer, Wulf Blankenfeldt,{dagger} Roger S. Goody,{dagger} Aymelt Itzen{dagger}

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.

Department of Physical Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, NRW, 44227, Germany.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: aymelt.itzen{at} (A.I.); roger.goody{at} (R.S.G.); wulf.blankenfeldt{at} (W.B.)

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