Download MendeleyStructural Insights Into the Dual Nucleotide Exchange and Gdi Displacement Activity of Sidm/Drra
Suh, H.Y., Lee, D.W., Lee, K.H., Ku, B., Choi, S.J., Woo, J.S., Kim, Y.G., Oh, B.H.(2010) EMBO J 29: 496
- PubMed: 19942850
- DOI: https://doi.org/10.1038/emboj.2009.347
- Primary Citation of Related Structures:
2WWX - PubMed 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 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.
Organizational Affiliation:
Department of Life Sciences and Center for Biomolecular Recognition, Pohang University of Science and Technology, Pohang, Kyungbuk, Korea.
