RabGDI displacement by DrrA from Legionella is a consequence of its guanine nucleotide exchange activity
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RabGDI displacement by DrrA from Legionella is a consequence of its guanine nucleotide exchange activity. / Schoebel, Stefan; Oesterlin, Lena Katharina; Blankenfeldt, Wulf; Goody, Roger Sidney; Itzen, Aymelt.
in: MOL CELL, Jahrgang 36, Nr. 6, 25.12.2009, S. 1060-72.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - RabGDI displacement by DrrA from Legionella is a consequence of its guanine nucleotide exchange activity
AU - Schoebel, Stefan
AU - Oesterlin, Lena Katharina
AU - Blankenfeldt, Wulf
AU - Goody, Roger Sidney
AU - Itzen, Aymelt
N1 - 2009 Elsevier Inc.
PY - 2009/12/25
Y1 - 2009/12/25
N2 - 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.
AB - 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.
KW - Bacterial Proteins
KW - Crystallography, X-Ray
KW - DNA-Binding Proteins
KW - Guanine Nucleotide Dissociation Inhibitors
KW - Guanine Nucleotide Exchange Factors
KW - Guanosine Diphosphate
KW - Guanosine Triphosphate
KW - Humans
KW - Legionella pneumophila
KW - Models, Molecular
KW - Molecular Sequence Data
KW - Multiprotein Complexes
KW - Protein Binding
KW - Protein Conformation
KW - rab1 GTP-Binding Proteins
KW - Journal Article
U2 - 10.1016/j.molcel.2009.11.014
DO - 10.1016/j.molcel.2009.11.014
M3 - SCORING: Journal article
C2 - 20064470
VL - 36
SP - 1060
EP - 1072
JO - MOL CELL
JF - MOL CELL
SN - 1097-2765
IS - 6
ER -