Structural insights into the dual nucleotide exchange and GDI displacement activity of SidM/DrrA.
EMBO J
; 29(2): 496-504, 2010 Jan 20.
Article
en En
| MEDLINE
| ID: mdl-19942850
ABSTRACT
GDP-bound prenylated Rabs, sequestered by GDI (GDP dissociation inhibitor) in the cytosol, are delivered to destined sub-cellular compartment and subsequently activated by GEFs (guanine nucleotide exchange factors) catalysing GDP-to-GTP exchange. The dissociation of GDI from Rabs is believed to require a GDF (GDI displacement factor). Only two RabGDFs, human PRA-1 and Legionella pneumophila SidM/DrrA, have been identified so far and the molecular mechanism of GDF is elusive. Here, we present the structure of a SidM/DrrA fragment possessing dual GEF and GDF activity in complex with Rab1. SidM/DrrA reconfigures the Switch regions of the GTPase domain of Rab1, as eukaryotic GEFs do toward cognate Rabs. Structure-based mutational analyses show that the surface of SidM/DrrA, catalysing nucleotide exchange, is involved in GDI1 displacement from prenylated Rab1GDP. In comparison with an eukaryotic GEF TRAPP I, this bacterial GEF/GDF exhibits high binding affinity for Rab1 with GDP retained at the active site, which appears as the key feature for the GDF activity of the protein.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Bacterianas
/
Enfermedad de los Legionarios
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Legionella pneumophila
/
Proteínas de Unión al GTP rab1
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Inhibidores de Disociación de Guanina Nucleótido
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Factores de Intercambio de Guanina Nucleótido
/
Proteínas de Unión al ADN
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
EMBO J
Año:
2010
Tipo del documento:
Article