3l0i

From Proteopedia

(Difference between revisions)

Revision as of 05:48, 10 February 2016

Complex structure of SidM/DrrA with the wild type Rab1

Structural highlights

3l0i is a 4 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.
Ligands:	,
NonStd Res:
Related:	3l0m
Gene:	sidM (ATCC 33152), RAB1A (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

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

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

Bacterial pathogens deliver effector proteins with diverse biochemical activities into host cells, thereby modulating various host functions. Legionella pneumophila hijacks host vesicle trafficking to avoid phagosome-lysosome fusion, a mechanism that is dependent on the Legionella Dot/Icm type IV secretion system. SidM/DrrA, a Legionella type IV effector, is important for the interactions of Legionella-containing vacuoles with host endoplasmic reticulum-derived vesicles. SidM is the only known protein that catalyzes both the exchange of GDP for GTP and GDI displacement from small GTPase Rab1. We determined the crystal structures of SidM alone (residues 317-647) and SidM (residues 193-550) in complex with nucleotide-free WT Rab1. The SidM structure contains an N-terminal helical domain with a potential new function, a Rab1-activation domain, and a C-terminal phosphatidylinositol 4-phosphate-binding P4M domain. The Rab1-activation domain has extensive strong interactions mainly with Rab1 switch I and II regions that undergo substantial conformational changes on SidM binding. Mutations of switch-contacting residues in SidM attenuate both the nucleotide exchange and GDI displacement activities. Structural comparisons of Rab1 in the SidM complex with Rab1-GDP and Ypt1-GDP in the GDI complex identify key conformational changes that disrupt the nucleotide and GDI binding of Rab1. Further biochemical and structural analyses reveal a unique mechanism of coupled GDP release and GDI displacement likely triggered by the SidM-induced drastic displacement of switch I of Rab1.

Structural mechanism of host Rab1 activation by the bifunctional Legionella type IV effector SidM/DrrA.,Zhu Y, Hu L, Zhou Y, Yao Q, Liu L, Shao F Proc Natl Acad Sci U S A. 2010 Mar 9;107(10):4699-704. Epub 2010 Feb 22. PMID:20176951^[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
↑ 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

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/3l0i"

@@ Line 2: / Line 2: @@
 <StructureSection load='3l0i' size='340' side='right' caption='[[3l0i]], [[Resolution|resolution]] 2.85&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3l0i]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Legionella_pneumophila Legionella pneumophila]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3L0I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3L0I FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3l0i]] is a 4 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=3L0I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3L0I FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3l0m|3l0m]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">sidM ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=446 Legionella pneumophila]), RAB1A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">sidM ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=446 ATCC 33152]), RAB1A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3l0i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3l0i OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3l0i RCSB], [http://www.ebi.ac.uk/pdbsum/3l0i 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=3l0i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3l0i OCA], [http://pdbe.org/3l0i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3l0i RCSB], [http://www.ebi.ac.uk/pdbsum/3l0i PDBsum]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/Q29ST3_LEGPN Q29ST3_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.<ref>PMID:16906144</ref> <ref>PMID:17952054</ref> <ref>PMID:20651120</ref>  [[http://www.uniprot.org/uniprot/RAB1A_HUMAN RAB1A_HUMAN]] Probably required for transit of protein from the ER through Golgi compartment. Binds GTP and GDP and possesses intrinsic GTPase activity.
+[[http://www.uniprot.org/uniprot/DRRA_LEGPN 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.<ref>PMID:16906144</ref> <ref>PMID:17952054</ref> <ref>PMID:20651120</ref>  [[http://www.uniprot.org/uniprot/RAB1A_HUMAN RAB1A_HUMAN]] Probably required for transit of protein from the ER through Golgi compartment. Binds GTP and GDP and possesses intrinsic GTPase activity.
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 19: / 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=3l0i ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 29: / Line 29: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3l0i" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Atcc 33152]]
-[[Category: Legionella pneumophila]]
+[[Category: Human]]
 [[Category: Shao, F]]
 [[Category: Zhu, Y]]

3l0i

From Proteopedia

Revision as of 05:48, 10 February 2016

Complex structure of SidM/DrrA with the wild type Rab1

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox