1. RabGDI Displacement by DrrA from Legionella Is a Consequence of Its Guanine Nucleotide Exchange Activity
- Author
-
Schoebel, Stefan, Oesterlin, Lena Katharina, Blankenfeldt, Wulf, Goody, Roger Sidney, and Itzen, Aymelt
- Subjects
- *
NUCLEOTIDES , *CYTOSOL , *LEGIONELLA pneumophila , *GUANOSINE triphosphatase , *ENZYME kinetics , *BIOLOGICAL membranes , *MOLECULAR biology - Abstract
Summary: 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. [Copyright &y& Elsevier]
- Published
- 2009
- Full Text
- View/download PDF