|
|
| (2 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| | + | |
| | ==Crystal structure of the GEF and P4M domain of DrrA/SidM from Legionella pneumophila== | | ==Crystal structure of the GEF and P4M domain of DrrA/SidM from Legionella pneumophila== |
| - | <StructureSection load='3n6o' size='340' side='right' caption='[[3n6o]], [[Resolution|resolution]] 2.50Å' scene=''> | + | <StructureSection load='3n6o' size='340' side='right'caption='[[3n6o]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3n6o]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Legionella_pneumophila Legionella pneumophila]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3N6O OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3N6O FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3n6o]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Legionella_pneumophila_subsp._pneumophila_str._Philadelphia_1 Legionella pneumophila subsp. pneumophila str. Philadelphia 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3N6O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3N6O FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DrrA, lpg2464 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=446 Legionella pneumophila])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3n6o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3n6o OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3n6o RCSB], [http://www.ebi.ac.uk/pdbsum/3n6o PDBsum]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3n6o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3n6o OCA], [https://pdbe.org/3n6o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3n6o RCSB], [https://www.ebi.ac.uk/pdbsum/3n6o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3n6o ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/Q5ZSQ3_LEGPH Q5ZSQ3_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.<ref>PMID:16824952</ref> <ref>PMID:17947549</ref> <ref>PMID:21822290</ref> <ref>PMID:20064470</ref> <ref>PMID:19942850</ref> <ref>PMID:20176951</ref> | + | [https://www.uniprot.org/uniprot/DRRA_LEGPH 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.<ref>PMID:16824952</ref> <ref>PMID:17947549</ref> <ref>PMID:21822290</ref> <ref>PMID:20064470</ref> <ref>PMID:19942850</ref> <ref>PMID:20176951</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | The DrrA protein of Legionella pneumophila is involved in mistargeting of endoplasmic reticulum-derived vesicles to Legionella-containing vacuoles through recruitment of the small GTPase Rab1. To this effect, DrrA binds specifically to phosphatidylinositol 4-phosphate (PtdIns(4)P) lipids on the cytosolic surface of the phagosomal membrane shortly after infection. In this study, we present the atomic structure of the PtdIns(4)P-binding domain of a protein (DrrA) from a human pathogen. A detailed kinetic investigation of its interaction with PtdIns(4)P reveals that DrrA binds to this phospholipid with, as yet unprecedented, high affinity, suggesting that DrrA can sense a very low abundance of the lipid.
| + | |
| - | | + | |
| - | High-affinity binding of phosphatidylinositol 4-phosphate by Legionella pneumophila DrrA.,Schoebel S, Blankenfeldt W, Goody RS, Itzen A EMBO Rep. 2010 Aug;11(8):598-604. Epub 2010 Jul 9. PMID:20616805<ref>PMID:20616805</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Legionella pneumophila]] | + | [[Category: Large Structures]] |
| - | [[Category: Blankenfeldt, W]] | + | [[Category: Legionella pneumophila subsp. pneumophila str. Philadelphia 1]] |
| - | [[Category: Goody, R S]] | + | [[Category: Blankenfeldt W]] |
| - | [[Category: Itzen, A]] | + | [[Category: Goody RS]] |
| - | [[Category: Schoebel, S]] | + | [[Category: Itzen A]] |
| - | [[Category: Gef]]
| + | [[Category: Schoebel S]] |
| - | [[Category: Lcv]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: P4m]]
| + | |
| - | [[Category: Phosphatidylinositol-4-phosphate]]
| + | |
| - | [[Category: Rab]]
| + | |
| - | [[Category: Rabgef]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
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]
References
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
|
