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2wwx

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Revision as of 14:59, 8 July 2020

Crystal structure of the SidM/DrrA(GEF/GDF domain)-Rab1(GTPase domain) complex

Structural highlights

2wwx is a 2 chain structure with sequence from Atcc 33152 and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	2fol
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[RAB1A_HUMAN] Probably required for transit of protein from the ER through Golgi compartment. Binds GTP and GDP and possesses intrinsic GTPase activity. [DRRA_LEGPN] 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]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

Structural insights into the dual nucleotide exchange and GDI displacement activity of SidM/DrrA.,Suh HY, Lee DW, Lee KH, Ku B, Choi SJ, Woo JS, Kim YG, Oh BH EMBO J. 2010 Jan 20;29(2):496-504. Epub 2009 Nov 26. PMID:19942850^[4]

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

References

↑ Murata T, Delprato A, Ingmundson A, Toomre DK, Lambright DG, Roy CR. The Legionella pneumophila effector protein DrrA is a Rab1 guanine nucleotide-exchange factor. Nat Cell Biol. 2006 Sep;8(9):971-7. Epub 2006 Aug 13. PMID:16906144 doi:10.1038/ncb1463
↑ Ingmundson A, Delprato A, Lambright DG, Roy CR. Legionella pneumophila proteins that regulate Rab1 membrane cycling. Nature. 2007 Nov 15;450(7168):365-9. Epub 2007 Oct 21. PMID:17952054 doi:10.1038/nature06336
↑ Muller MP, Peters H, Blumer J, Blankenfeldt W, Goody RS, Itzen A. The Legionella effector protein DrrA AMPylates the membrane traffic regulator Rab1b. Science. 2010 Aug 20;329(5994):946-9. Epub 2010 Jul 22. PMID:20651120 doi:10.1126/science.1192276
↑ 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

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2wwx"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the SidM/DrrA(GEF/GDF domain)-Rab1(GTPase domain) complex==
-<StructureSection load='2wwx' size='340' side='right' caption='[[2wwx]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
+<StructureSection load='2wwx' size='340' side='right'caption='[[2wwx]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2wwx]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_33152 Atcc 33152] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WWX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2WWX FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2wwx]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_33152 Atcc 33152] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WWX OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2WWX FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2fol|2fol]]</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=2wwx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wwx OCA], [http://pdbe.org/2wwx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2wwx RCSB], [http://www.ebi.ac.uk/pdbsum/2wwx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2wwx ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2wwx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wwx OCA], [http://pdbe.org/2wwx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2wwx RCSB], [http://www.ebi.ac.uk/pdbsum/2wwx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2wwx ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 34: / Line 34: @@
 [[Category: Atcc 33152]]
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Lee, D W]]
 [[Category: Oh, B H]]

2wwx

From Proteopedia

Revision as of 14:59, 8 July 2020

Crystal structure of the SidM/DrrA(GEF/GDF domain)-Rab1(GTPase domain) complex

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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