3jz9

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Crystal structure of the GEF domain of DrrA/SidM from Legionella pneumophila

Structural highlights

3jz9 is a 1 chain structure with sequence from Legionella pneumophila subsp. pneumophila str. Philadelphia 1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.8Å
Ligands:MSE
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DRRA_LEGPH Virulence effector that plays a key role in hijacking the host vesicular trafficking by recruiting the small guanosine triphosphatase (GTPase) Rab1 to the cytosolic face of the Legionella-containing vacuole (LCVs). Acts as a GDP-GTP exchange factor (GEF) for the small GTPase Rab1 (RAB1A, RAB1B or RAB1C), thereby converting Rab1 to an active GTP-bound state, leading to the incorporation of Rab1 into LCVs. Also shows RabGDI displacement factor (GDF) activity; however, this probably represents a passive activity following the GEF activity. Also acts as an adenylyltransferase by mediating the addition of adenosine 5'-monophosphate (AMP) to 'Tyr-77' of host RAB1B, thereby rendering RAB1B constitutively active. Also has adenylyltransferase activity towards Rab6 and Rab35. Also displays guanylyltransferase activity by mediating the addition of guanosine 5'-monophosphate (GMP) to host RAB1B in vitro; however such activity remains uncertain in vivo. Specifically binds phosphatidylinositol 4-phosphate (PtdIns(4)P) lipids on the cytosolic surface of the phagosomal membrane shortly after infection.[1] [2] [3] [4] [5] [6]

Publication Abstract from PubMed

Prenylated Rab proteins exist in the cytosol as soluble, high-affinity complexes with GDI that need to be disrupted for membrane attachment and targeting of Rab proteins. The Legionella pneumophila protein DrrA displaces GDI from Rab1:GDI complexes, incorporating Rab1 into Legionella-containing vacuoles and activating Rab1 by exchanging GDP for GTP. Here, we present the crystal structure of a complex between the GEF domain of DrrA and Rab1 and a detailed kinetic analysis of this exchange. DrrA efficiently catalyzes nucleotide exchange and mimics the general nucleotide exchange mechanism of mammalian GEFs for Ras-like GTPases. We show that the GEF activity of DrrA is sufficient to displace prenylated Rab1 from the Rab1:GDI complex. Thus, apparent GDI displacement by DrrA is linked directly to nucleotide exchange, suggesting a basic model for GDI displacement and specificity of Rab localization that does not require discrete GDI displacement activity.

RabGDI displacement by DrrA from Legionella is a consequence of its guanine nucleotide exchange activity.,Schoebel S, Oesterlin LK, Blankenfeldt W, Goody RS, Itzen A Mol Cell. 2009 Dec 25;36(6):1060-72. PMID:20064470[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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References

  1. ↑ Machner MP, Isberg RR. Targeting of host Rab GTPase function by the intravacuolar pathogen Legionella pneumophila. Dev Cell. 2006 Jul;11(1):47-56. PMID:16824952 doi:10.1016/j.devcel.2006.05.013
  2. ↑ Machner MP, Isberg RR. A bifunctional bacterial protein links GDI displacement to Rab1 activation. Science. 2007 Nov 9;318(5852):974-7. Epub 2007 Oct 18. PMID:17947549
  3. ↑ Mukherjee S, Liu X, Arasaki K, McDonough J, Galan JE, Roy CR. Modulation of Rab GTPase function by a protein phosphocholine transferase. Nature. 2011 Aug 7;477(7362):103-6. doi: 10.1038/nature10335. PMID:21822290 doi:10.1038/nature10335
  4. ↑ Schoebel S, Oesterlin LK, Blankenfeldt W, Goody RS, Itzen A. RabGDI displacement by DrrA from Legionella is a consequence of its guanine nucleotide exchange activity. Mol Cell. 2009 Dec 25;36(6):1060-72. PMID:20064470 doi:10.1016/j.molcel.2009.11.014
  5. ↑ Suh HY, Lee DW, Lee KH, Ku B, Choi SJ, Woo JS, Kim YG, Oh BH. Structural insights into the dual nucleotide exchange and GDI displacement activity of SidM/DrrA. EMBO J. 2010 Jan 20;29(2):496-504. Epub 2009 Nov 26. PMID:19942850 doi:10.1038/emboj.2009.347
  6. ↑ Zhu Y, Hu L, Zhou Y, Yao Q, Liu L, Shao F. Structural mechanism of host Rab1 activation by the bifunctional Legionella type IV effector SidM/DrrA. Proc Natl Acad Sci U S A. 2010 Mar 9;107(10):4699-704. Epub 2010 Feb 22. PMID:20176951 doi:10.1073/pnas.0914231107
  7. ↑ Schoebel S, Oesterlin LK, Blankenfeldt W, Goody RS, Itzen A. RabGDI displacement by DrrA from Legionella is a consequence of its guanine nucleotide exchange activity. Mol Cell. 2009 Dec 25;36(6):1060-72. PMID:20064470 doi:10.1016/j.molcel.2009.11.014

Contents


PDB ID 3jz9

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