A Bifunctional Bacterial Protein Links Gdi Displacement to Rab1 Activation

• Published in: Science (American Association for the Advancement of Science) 2007-11, Vol.318 (5852), p.974-977
• Main Authors: Machner, Matthias P., Isberg, Ralph R.
• Format: Article
• Language: English
• Subjects: Amino acids; Antibodies; Bacteria; Bacterial Proteins - chemistry; Bacterial Proteins - metabolism; Bacteriology; Biological and medical sciences; Cellular biology; COS cells; Cytoplasm - metabolism; Cytosol; Fundamental and applied biological sciences. Psychology; Guanine nucleotide dissociation inhibitors; Guanine Nucleotide Dissociation Inhibitors - metabolism; Guanine Nucleotide Exchange Factors - metabolism; Guanosine 5'-O-(3-Thiotriphosphate) - metabolism; Guanosine Diphosphate - metabolism; Humans; Legionella pneumophila; Legionella pneumophila - metabolism; Legionnaires' disease; Liposomes; Membranes; Microbiology; Miscellaneous; Nucleotides; Physiological regulation; Protein Binding; Protein Structure, Tertiary; Proteins; rab1 GTP-Binding Proteins - metabolism; Recombinant Proteins - chemistry; Recombinant Proteins - metabolism; rho-Specific Guanine Nucleotide Dissociation Inhibitors; Vacuoles; Vacuoles - metabolism; Vacuoles - microbiology
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1149121

Rab guanosine triphosphatases (GTPases) regulate vesicle trafficking in eukaryotic cells by reversibly associating with lipid membranes. Inactive Rab GTPases are maintained in the cytosol by binding to GDP-dissociation inhibitor (GDI). It is believed that specialized proteins are required to displace GDI from Rab GTPases before Rab activation by guanosine diphosphate--guanosine 5′-triphosphate (GDP-GTP) exchange factors (GEFs). Here, we found that SidM from Legionella pneumophila could act as both GEF and GDI-displacement factor (GDF) for Rab1. Rab1 released from GDI was inserted into liposomal membranes and was used as a substrate for SidM-mediated nucleotide exchange. During host cell infection, recruitment of Rab1 to Legionella-containing vacuoles depended on the GDF activity of SidM. Thus, GDF and GEF activity can be promoted by a single protein, and GDF activity can coordinate Rab1 recruitment from the GDI-bound pool.