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

نویسندگان

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

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.

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عنوان ژورنال:
  • The EMBO journal

دوره 29 2  شماره 

صفحات  -

تاریخ انتشار 2010