5o74: Difference between revisions
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==Crystal structure of human Rab1b covalently bound to the GEF domain of DrrA/SidM from Legionella pneumophila in the presence of GDP== | ==Crystal structure of human Rab1b covalently bound to the GEF domain of DrrA/SidM from Legionella pneumophila in the presence of GDP== | ||
<StructureSection load='5o74' size='340' side='right' caption='[[5o74]], [[Resolution|resolution]] 2.50Å' scene=''> | <StructureSection load='5o74' size='340' side='right'caption='[[5o74]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5o74]] is a 12 chain structure with sequence from [ | <table><tr><td colspan='2'>[[5o74]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Legionella_pneumophila Legionella pneumophila]. 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 [https://proteopedia.org/fgij/fg.htm?mol=5O74 FirstGlance]. <br> | ||
</td></tr><tr id=' | </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=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9MN:(2~{S})-2-azanyl-6-(6-bromanylhexanoylamino)hexanoic+acid'>9MN</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene></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=5o74 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o74 OCA], [https://pdbe.org/5o74 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5o74 RCSB], [https://www.ebi.ac.uk/pdbsum/5o74 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5o74 ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://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> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 20: | Line 19: | ||
</div> | </div> | ||
<div class="pdbe-citations 5o74" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5o74" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Ras-related protein Rab 3D structures|Ras-related protein Rab 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Legionella pneumophila]] | [[Category: Legionella pneumophila]] | ||
[[Category: | [[Category: Cigler M]] | ||
[[Category: Fottner M]] | |||
[[Category: Goody RS]] | |||
[[Category: Horn-Ghetko D]] | |||
[[Category: Itzen A]] | |||
[[Category: Lang K]] | |||
[[Category: Mueller MP]] | |||
[[Category: Mueller T]] | |||
[[Category: Von Wrisberg MK]] | |||
Latest revision as of 22:10, 29 November 2023
Crystal structure of human Rab1b covalently bound to the GEF domain of DrrA/SidM from Legionella pneumophila in the presence of GDPCrystal structure of human Rab1b covalently bound to the GEF domain of DrrA/SidM from Legionella pneumophila in the presence of GDP
Structural highlights
FunctionDRRA_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] Publication Abstract from PubMedThe 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[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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