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

doi:10.1016/j.molcel.2009.11.014

RabGDI displacement by DrrA from Legionella is a consequence of its guanine nucleotide exchange activity

Mol Cell. 2009 Dec 25;36(6):1060-72. doi: 10.1016/j.molcel.2009.11.014.

Authors

Stefan Schoebel¹, Lena Katharina Oesterlin, Wulf Blankenfeldt, Roger Sidney Goody, Aymelt Itzen

Affiliation

¹ Department of Physical Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, NRW, Germany.

PMID: 20064470
DOI: 10.1016/j.molcel.2009.11.014

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.

2009 Elsevier Inc.

MeSH terms

Bacterial Proteins / chemistry
Bacterial Proteins / genetics
Bacterial Proteins / metabolism*
Crystallography, X-Ray
DNA-Binding Proteins / chemistry
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism*
Guanine Nucleotide Dissociation Inhibitors / genetics
Guanine Nucleotide Dissociation Inhibitors / metabolism*
Guanine Nucleotide Exchange Factors / genetics
Guanine Nucleotide Exchange Factors / metabolism
Guanosine Diphosphate / metabolism*
Guanosine Triphosphate / metabolism*
Humans
Legionella pneumophila / metabolism*
Models, Molecular
Molecular Sequence Data
Multiprotein Complexes / chemistry
Multiprotein Complexes / metabolism
Protein Binding
Protein Conformation
rab1 GTP-Binding Proteins / chemistry
rab1 GTP-Binding Proteins / genetics
rab1 GTP-Binding Proteins / metabolism*

Substances

Bacterial Proteins
DNA-Binding Proteins
DrrA protein, Bacteria
Guanine Nucleotide Dissociation Inhibitors
Guanine Nucleotide Exchange Factors
Multiprotein Complexes
Guanosine Diphosphate
Guanosine Triphosphate
rab1 GTP-Binding Proteins

Associated data

PDB/3JZ9
PDB/3JZA