5oec: Difference between revisions
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==Human Rab32 (18-201):GDP in complex with Salmonella GtgE (21-214) C45A mutant== | |||
<StructureSection load='5oec' size='340' side='right'caption='[[5oec]], [[Resolution|resolution]] 2.30Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5oec]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Salmonella_enterica Salmonella enterica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OEC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OEC FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MLY:N-DIMETHYL-LYSINE'>MLY</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=5oec FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5oec OCA], [https://pdbe.org/5oec PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5oec RCSB], [https://www.ebi.ac.uk/pdbsum/5oec PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5oec ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q6EAT3_SALER Q6EAT3_SALER] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Salmonella infections require the delivery of bacterial effectors into the host cell that alter the regulation of host defense mechanisms. The secreted cysteine protease GtgE from S. Typhimurium manipulates vesicular trafficking by modifying the Rab32 subfamily via cleaving the regulatory switch I region. Here we present a comprehensive biochemical, structural, and computational characterization of GtgE in complex with Rab32. Interestingly, GtgE solely processes the inactive GDP-bound GTPase. The crystal structure of the Rab32:GDP substrate in complex with the inactive mutant GtgEC45A reveals the molecular basis of substrate recognition. In combination with atomistic molecular dynamics simulations, the structural determinants for protein and activity-state specificity are identified. Mutations in a central interaction hub lead to loss of the strict GDP specificity. Our findings shed light on the sequence of host cell manipulation events during Salmonella infection and provide an explanation for the dependence on the co-secreted GTPase activating protein SopD2. | |||
The protease GtgE from Salmonella exclusively targets inactive Rab GTPases.,Wachtel R, Brauning B, Mader SL, Ecker F, Kaila VRI, Groll M, Itzen A Nat Commun. 2018 Jan 3;9(1):44. doi: 10.1038/s41467-017-02110-1. PMID:29298974<ref>PMID:29298974</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5oec" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: Braeuning | ==See Also== | ||
[[Category: | *[[Ras-related protein Rab 3D structures|Ras-related protein Rab 3D structures]] | ||
[[Category: Groll | == References == | ||
[[Category: | <references/> | ||
[[Category: Mader | __TOC__ | ||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Salmonella enterica]] | |||
[[Category: Braeuning B]] | |||
[[Category: Ecker F]] | |||
[[Category: Groll M]] | |||
[[Category: Itzen A]] | |||
[[Category: Kaila VRI]] | |||
[[Category: Mader SL]] | |||
[[Category: Wachtel R]] |
Latest revision as of 19:46, 13 December 2023
Human Rab32 (18-201):GDP in complex with Salmonella GtgE (21-214) C45A mutantHuman Rab32 (18-201):GDP in complex with Salmonella GtgE (21-214) C45A mutant
Structural highlights
FunctionPublication Abstract from PubMedSalmonella infections require the delivery of bacterial effectors into the host cell that alter the regulation of host defense mechanisms. The secreted cysteine protease GtgE from S. Typhimurium manipulates vesicular trafficking by modifying the Rab32 subfamily via cleaving the regulatory switch I region. Here we present a comprehensive biochemical, structural, and computational characterization of GtgE in complex with Rab32. Interestingly, GtgE solely processes the inactive GDP-bound GTPase. The crystal structure of the Rab32:GDP substrate in complex with the inactive mutant GtgEC45A reveals the molecular basis of substrate recognition. In combination with atomistic molecular dynamics simulations, the structural determinants for protein and activity-state specificity are identified. Mutations in a central interaction hub lead to loss of the strict GDP specificity. Our findings shed light on the sequence of host cell manipulation events during Salmonella infection and provide an explanation for the dependence on the co-secreted GTPase activating protein SopD2. The protease GtgE from Salmonella exclusively targets inactive Rab GTPases.,Wachtel R, Brauning B, Mader SL, Ecker F, Kaila VRI, Groll M, Itzen A Nat Commun. 2018 Jan 3;9(1):44. doi: 10.1038/s41467-017-02110-1. PMID:29298974[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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