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Structural insights into the dual nucleotide exchange and GDI displacement activity of SidM/DrrA

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 requ...

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Published in:The EMBO journal 2010-01, Vol.29 (2), p.496-504
Main Authors: Suh, Hye-Young, Lee, Dong-Won, Lee, Kwang-Hoon, Ku, Bonsu, Choi, Sung-Jin, Woo, Jae-Sung, Kim, Yeon-Gil, Oh, Byung-Ha
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cited_by cdi_FETCH-LOGICAL-c6007-2f8815b14f81a2dd2085dd5b4e2b4d6354ca1c9eced2e18e1a1675b99915bcba3
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container_title The EMBO journal
container_volume 29
creator Suh, Hye-Young
Lee, Dong-Won
Lee, Kwang-Hoon
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Kim, Yeon-Gil
Oh, Byung-Ha
description 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 Rab1:GDP. 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.
doi_str_mv 10.1038/emboj.2009.347
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subjects Amino Acid Sequence
Bacterial Proteins - chemistry
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
Catalysis
Cellular biology
DNA-Binding Proteins - chemistry
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
EMBO37
EMBO40
GDF
GDI
GEF
Guanine Nucleotide Dissociation Inhibitors - metabolism
Guanine Nucleotide Exchange Factors - chemistry
Guanine Nucleotide Exchange Factors - genetics
Guanine Nucleotide Exchange Factors - metabolism
Guanosine Diphosphate - metabolism
Guanosine Triphosphate - metabolism
Humans
Inhibitor drugs
Legionella pneumophila
Legionella pneumophila - metabolism
Legionnaires' Disease - metabolism
Liposomes - metabolism
Magnesium - metabolism
Models, Molecular
Molecular biology
Molecular Sequence Data
Mutation
p-Rab1
Point Mutation
Protein Binding
Protein Conformation
rab1 GTP-Binding Proteins - metabolism
rho-Specific Guanine Nucleotide Dissociation Inhibitors
Sequence Alignment
SidM/DrrA
Substrate Specificity
title Structural insights into the dual nucleotide exchange and GDI displacement activity of SidM/DrrA
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