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5o74

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Revision as of 07:43, 6 December 2017

Crystal structure of human Rab1b covalently bound to the GEF domain of DrrA/SidM from Legionella pneumophila in the presence of GDP

Structural highlights

5o74 is a 12 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:
Gene:	drrA, sidM (ATCC 33152), RAB1B (HUMAN), RAB1B (ATCC 33152)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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] [RAB1B_HUMAN] Protein transport. Regulates vesicular transport between the endoplasmic reticulum and successive Golgi compartments.^[4]

Publication Abstract from PubMed

The characterization of low-affinity protein complexes is challenging due to their dynamic nature. Here we present a method to stabilize transient protein complexes in vivo by generating a covalent and conformationally flexible bridge between the interaction partners. A highly active pyrrolysyl tRNA synthetase mutant directs the incorporation of unnatural amino acids bearing bromoalkyl moieties (BrCnK) into proteins. We demonstrate for the first time that low-affinity protein complexes between BrCnK-containing proteins and their binding partners can be stabilized in vivo in bacterial and mammalian cells. Using this approach we determined the crystal structure of a transient GDP-bound complex between a small G-protein and its nucleotide exchange factor. We envision that this approach will prove valuable as a general tool for validating and characterizing protein-protein interactions in vitro and in vivo.

Proximity-triggered covalent stabilization of low-affinity protein complexes in vitro and in vivo.,Cigler M, Muller TG, Horn-Ghetko D, von Wrisberg MK, Fottner M, Goody RS, Itzen A, Muller MP, Lang K Angew Chem Int Ed Engl. 2017 Sep 28. doi: 10.1002/anie.201706927. PMID:28960788^[5]

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
↑ 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
↑ Cigler M, Muller TG, Horn-Ghetko D, von Wrisberg MK, Fottner M, Goody RS, Itzen A, Muller MP, Lang K. Proximity-triggered covalent stabilization of low-affinity protein complexes in vitro and in vivo. Angew Chem Int Ed Engl. 2017 Sep 28. doi: 10.1002/anie.201706927. PMID:28960788 doi:http://dx.doi.org/10.1002/anie.201706927

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5o74"

@@ Line 3: / Line 3: @@
 <StructureSection load='5o74' size='340' side='right' caption='[[5o74]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5o74]] is a 12 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5O74 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5O74 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5o74]] is a 12 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=5O74 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5O74 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene></td></tr>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=9MN:'>9MN</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">drrA, sidM ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=446 ATCC 33152]), RAB1B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), RAB1B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=446 ATCC 33152])</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=5o74 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o74 OCA], [http://pdbe.org/5o74 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5o74 RCSB], [http://www.ebi.ac.uk/pdbsum/5o74 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5o74 ProSAT]</span></td></tr>
 </table>
@@ Line 23: / Line 24: @@
 __TOC__
 </StructureSection>
+[[Category: Atcc 33152]]
+[[Category: Human]]
 [[Category: Cigler, M]]
 [[Category: Fottner, M]]

5o74

From Proteopedia

Revision as of 07:43, 6 December 2017

Crystal structure of human Rab1b covalently bound to the GEF domain of DrrA/SidM from Legionella pneumophila in the presence of GDP

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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