RabGDI Displacement by DrrA from Legionella Is a Consequence of Its Guanine Nucleotide Exchange Activity

Stefan Schoebel, Lena Katharina Oesterlin, Wulf Blankenfeldt, Roger Sidney Goody, Aymelt Itzen

Research output: Contribution to journalArticlepeer-review

146 Scopus citations

Abstract

Prenylated Rab proteins exist in the cytosol as soluble, high-affinity complexes with GDI that need to be disrupted for membrane attachment and targeting of Rab proteins. The Legionella pneumophila protein DrrA displaces GDI from Rab1:GDI complexes, incorporating Rab1 into Legionella-containing vacuoles and activating Rab1 by exchanging GDP for GTP. Here, we present the crystal structure of a complex between the GEF domain of DrrA and Rab1 and a detailed kinetic analysis of this exchange. DrrA efficiently catalyzes nucleotide exchange and mimics the general nucleotide exchange mechanism of mammalian GEFs for Ras-like GTPases. We show that the GEF activity of DrrA is sufficient to displace prenylated Rab1 from the Rab1:GDI complex. Thus, apparent GDI displacement by DrrA is linked directly to nucleotide exchange, suggesting a basic model for GDI displacement and specificity of Rab localization that does not require discrete GDI displacement activity.

Original languageEnglish
Pages (from-to)1060-1072
Number of pages13
JournalMolecular Cell
Volume36
Issue number6
DOIs
StatePublished - 24 Dec 2009
Externally publishedYes

Keywords

  • SIGNALING

Fingerprint

Dive into the research topics of 'RabGDI Displacement by DrrA from Legionella Is a Consequence of Its Guanine Nucleotide Exchange Activity'. Together they form a unique fingerprint.

Cite this