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3jza

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Revision as of 22:50, 5 August 2016

Crystal structure of human Rab1b in complex with the GEF domain of DrrA/SidM from Legionella pneumophila

Structural highlights

3jza is a 2 chain structure with sequence from Human and Legph. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	3jz9
Gene:	RAB1B (HUMAN), lpg2464 (LEGPH)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[RAB1B_HUMAN] Protein transport. Regulates vesicular transport between the endoplasmic reticulum and successive Golgi compartments.^[1] [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.^[2] ^[3] ^[4] ^[5] ^[6] ^[7]

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

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^[8]

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

References

↑ Overmeyer JH, Wilson AL, Erdman RA, Maltese WA. The putative "switch 2" domain of the Ras-related GTPase, Rab1B, plays an essential role in the interaction with Rab escort protein. Mol Biol Cell. 1998 Jan;9(1):223-35. PMID:9437002
↑ 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
↑ 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

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/3jza"

@@ Line 1: / Line 1: @@
 ==Crystal structure of human Rab1b in complex with the GEF domain of DrrA/SidM from Legionella pneumophila==
 <StructureSection load='3jza' size='340' side='right' caption='[[3jza]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3jza]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://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=3JZA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3JZA FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3jza]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Legph Legph]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3JZA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3JZA FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3jz9|3jz9]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RAB1B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), lpg2464 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=272624 Legionella pneumophila subsp. pneumophila str. Philadelphia 1])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RAB1B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), lpg2464 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=272624 LEGPH])</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=3jza FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3jza OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3jza RCSB], [http://www.ebi.ac.uk/pdbsum/3jza PDBsum]</span></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=3jza FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3jza OCA], [http://pdbe.org/3jza PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3jza RCSB], [http://www.ebi.ac.uk/pdbsum/3jza PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3jza ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/RAB1B_HUMAN RAB1B_HUMAN]] Protein transport. Regulates vesicular transport between the endoplasmic reticulum and successive Golgi compartments.<ref>PMID:9437002</ref>  [[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>
+[[http://www.uniprot.org/uniprot/RAB1B_HUMAN RAB1B_HUMAN]] Protein transport. Regulates vesicular transport between the endoplasmic reticulum and successive Golgi compartments.<ref>PMID:9437002</ref>  [[http://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>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 18: / Line 19: @@
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3jza ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 28: / Line 29: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3jza" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
-[[Category: Legionella pneumophila subsp. pneumophila str. philadelphia 1]]
+[[Category: Legph]]
 [[Category: Blankenfeldt, W]]
 [[Category: Goody, R S]]

3jza

From Proteopedia

Revision as of 22:50, 5 August 2016

Crystal structure of human Rab1b in complex with the GEF domain of DrrA/SidM from Legionella pneumophila

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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