View source for 5swj


==Crystal Structure of ATPase delta1-79 Spa47==
<StructureSection load='5swj' size='340' side='right'caption='[[5swj]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5swj]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Shigella_flexneri Shigella flexneri]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5SWJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5SWJ 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]] 2.401&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=5swj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5swj OCA], [https://pdbe.org/5swj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5swj RCSB], [https://www.ebi.ac.uk/pdbsum/5swj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5swj ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SCTN_SHIFL SCTN_SHIFL] ATPase component of the type III secretion system (T3SS), also called injectisome, which is used to inject bacterial effector proteins into eukaryotic host cells (PubMed:26947936, PubMed:27770024, PubMed:29595954). Acts as a molecular motor to provide the energy that is required for the export of proteins (Probable). Required for type III secretion apparatus (T3SA) formation, proper protein secretion, host cell invasion and virulence (PubMed:26947936, PubMed:27770024, PubMed:31162724). May play a critical role in T3SS substrate recognition, disassembly of the effector/chaperone complex and unfolding of the effector in an ATP-dependent manner prior to secretion (By similarity).[UniProtKB:P0A1B9]<ref>PMID:26947936</ref> <ref>PMID:27770024</ref> <ref>PMID:29595954</ref> <ref>PMID:31162724</ref> <ref>PMID:26947936</ref> <ref>PMID:27770024</ref> 
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== Publication Abstract from PubMed ==
Like many Gram-negative pathogens, Shigella rely on a complex type three secretion system (T3SS) to inject effector proteins into host cells, take over host functions, and ultimately establish infection. Despite these critical roles, the energetics and regulatory mechanisms controlling the T3SS and pathogen virulence remain largely unclear. In this study, we present a series of high-resolution crystal structures of Spa47 and use the structures to model an activated Spa47 oligomer, finding that ATP hydrolysis may be supported by specific sidechain contributions from adjacent protomers within the complex. Follow-up mutagenesis experiments targeting the predicted active site residues validate the oligomeric model and determined that each of the tested residues are essential for Spa47 ATPase activity, though they are not directly responsible for stable oligomer formation. While an N-terminal domain truncation was necessary for crystal formation, it resulted in strictly monomeric Spa47 that is unable to hydrolyze ATP, despite maintaining the canonical ATPase core structure and active site residues. Coupled with studies of ATPase inactive full-length Spa47 point mutants, we find that Spa47 oligomerization and ATP hydrolysis are needed for complete T3SS apparatus formation, a proper translocator secretion profile, and Shigella virulence. This work represents the first structure-function characterization of Spa47, uniquely complementing the multitude of included Shigella T3SS phenotype assays and providing a more complete understanding of T3SS ATPase-mediated pathogen virulence. Additionally, these findings provide a strong platform for follow-up studies evaluating regulation of Spa47 oligomerization in vivo as a much needed means of treating and perhaps preventing shigellosis.

Structural and Biochemical Characterization of Spa47 Provides Mechanistic Insight into Type III Secretion System ATPase Activation and Shigella Virulence Regulation.,Burgess JL, Burgess RA, Morales Y, Bouvang JM, Johnson SJ, Dickenson NE J Biol Chem. 2016 Oct 21. pii: jbc.M116.755256. PMID:27770024<ref>PMID:27770024</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5swj" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Shigella flexneri]]
[[Category: Burgess JL]]
[[Category: Burgess RA]]
[[Category: Dickenson NE]]
[[Category: Johnson SJ]]
[[Category: Morales Y]]