View source for 7rqh


==Crystal Structure of carboxyl-terminal processing protease A mutant S302A, CtpA_S302A, of Pseudomonas aeruginosa==
<StructureSection load='7rqh' size='340' side='right'caption='[[7rqh]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7rqh]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa_PAO1 Pseudomonas aeruginosa PAO1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RQH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RQH 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]] 3.2&#8491;</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=7rqh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rqh OCA], [https://pdbe.org/7rqh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rqh RCSB], [https://www.ebi.ac.uk/pdbsum/7rqh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rqh ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q9HU50_PSEAE Q9HU50_PSEAE] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Pseudomonas aeruginosa CtpA is a carboxyl-terminal processing protease that partners with the outer membrane lipoprotein LbcA to degrade at least five cell wall-associated proteins, four of which are cell wall hydrolases. This activity plays an important role in supporting P. aeruginosa virulence in a mouse model of acute pneumonia. However, almost nothing is known about the molecular mechanisms underlying CtpA and LbcA function. Here, we used structural analysis to show that CtpA alone assembles into an inactive hexamer comprising a trimer of dimers, which limits its substrate access and prevents nonspecific degradation. The adaptor protein LbcA is a right-handed open spiral with 11 tetratricopeptide repeats, which might wrap around a substrate to deliver it to CtpA for degradation. By structure-guided mutagenesis and functional assays, we also showed that the interfaces of the CtpA trimer of dimers and an N-terminal helix of LbcA are important for LbcA-mediated substrate degradation by CtpA both in vitro and in vivo. This work improves our understanding of the molecular mechanism of the LbcA-CtpA proteolytic system and reveals some striking differences from the arrangements found in some other bacterial CTPs. IMPORTANCE Carboxyl-terminal processing proteases (CTPs) are found in all three domains of life. In bacteria, some CTPs have been associated with virulence, raising the possibility that they could be therapeutic targets. However, relatively little is known about their molecular mechanisms of action. In Pseudomonas aeruginosa, CtpA supports virulence by working in complex with the outer membrane lipoprotein LbcA to degrade cell wall hydrolases. Here, we report structure-function analyses of CtpA and LbcA, which reveals that CtpA assembles into an inactive hexamer comprising a trimer of dimers. LbcA is monomeric, with the first N-terminal helix important for binding to and activating CtpA, followed by a spiral structure composed of 11 tetratricopeptide repeats, which could wrap around a substrate for delivery to CtpA. This work reveals a unique mutimeric arrangement for a CTP and insight into how the important LbcA-CtpA proteolytic system functions.

Pseudomonas aeruginosa C-Terminal Processing Protease CtpA Assembles into a Hexameric Structure That Requires Activation by a Spiral-Shaped Lipoprotein-Binding Partner.,Hsu HC, Wang M, Kovach A, Darwin AJ, Li H mBio. 2022 Jan 18:e0368021. doi: 10.1128/mbio.03680-21. PMID:35038915<ref>PMID:35038915</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7rqh" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Pseudomonas aeruginosa PAO1]]
[[Category: Hsu HC]]
[[Category: Li H]]