A Bifunctional Bacterial Protein Links Gdi Displacement to Rab1 Activation

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 displac...

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Bibliographic Details
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
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Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1149121