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

Hye Young Suh, Dong Won Lee, Kwang Hoon Lee, Bonsu Ku, Sung Jin Choi, Jae Sung Woo, Yeon Gil Kim, Byung Ha Oh

Research output: Contribution to journalArticle

57 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)496-504
Number of pages9
JournalEMBO Journal
Volume29
Issue number2
DOIs
Publication statusPublished - 2010 Jan
Externally publishedYes

Keywords

  • GDF
  • GDI
  • GEF
  • P-Rab1
  • SidM/DrrA

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Suh, H. Y., Lee, D. W., Lee, K. H., Ku, B., Choi, S. J., Woo, J. S., Kim, Y. G., & Oh, B. H. (2010). Structural insights into the dual nucleotide exchange and GDI displacement activity of SidM/DrrA. EMBO Journal, 29(2), 496-504. https://doi.org/10.1038/emboj.2009.347