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4zqu

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CdiA-CT/CdiI toxin and immunity complex from Yersinia pseudotuberculosis

Structural highlights

4zqu is a 2 chain structure with sequence from Salmonella enterica subsp. enterica serovar Rubislaw str. ATCC 10717 and Yersinia pseudotuberculosis YPIII. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.09Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CDIA_YERPY Toxic component of a toxin-immunity protein module, which functions as a cellular contact-dependent growth inhibition (CDI) system. CDI modules allow bacteria to communicate with and inhibit the growth of closely related neighboring bacteria in a contact-dependent fashion. The C-terminal 123 residues (954-1077) has DNase activity in the presence of Zn(2+), converting supercoiled DNA into open-circular form. Toxic activity is neutralized by coexpression of the cognate immunity protein CdiI-YPIII, but not by non-cognate immunity proteins from other toxin-immunity modules. Expression of the DNase domain as a chimera allows bacteria to attack other non-immune bacteria which become filamentous and have lost DNA staining.^[1] The CdiA protein is thought to be exported from the cell through the central lumen of CdiB, the other half of its two-partner system (TPS). The TPS domain probably remains associated with CdiB while the FHA-1 domain forms an extended filament with the receptor-binding domain (RBD) at its extremity; in the secretion arrested state the C-terminus of the RBD and YP domains form a hairpin-like structure as the FHA-2, PT and CT domains are periplasmic. The YP domain is probably responsible for this arrest at the point where it re-enters the host cell periplasm. Upon binding to a target cell outer membrane receptor a signal is transmitted to activate secretion. The filament elongates slightly, the rest of CdiA is secreted and the FHA-2 domain becomes stably associated with the target cell's outer membrane where it facilitates entry of the toxic CT domain into the target cell periplasm. From there the toxic CT domain is cleaved and gains access to the target cell cytoplasm via an inner membrane protein.

Publication Abstract from PubMed

Contact-dependent growth inhibition (CDI) is a widespread mechanism of inter-bacterial competition mediated by the CdiB/CdiA family of two-partner secretion proteins. CdiA effectors carry diverse C-terminal toxin domains (CdiA-CT), which are delivered into neighboring target cells to inhibit growth. CDI(+) bacteria also produce CdiI immunity proteins that bind specifically to cognate CdiA-CT toxins and protect the cell from auto-inhibition. Here, we compare the structures of homologous CdiA-CT/CdiI complexes from Escherichia coli EC869 and Yersinia pseudotuberculosis YPIII to explore the evolution of CDI toxin/immunity protein interactions. Both complexes share an unusual beta-augmentation interaction, in which the toxin domain extends a beta-hairpin into the immunity protein to complete a six-stranded anti-parallel sheet. However, the specific contacts differ substantially between the two complexes. The EC869 beta-hairpin interacts mainly through direct H-bond and ion-pair interactions, whereas the YPIII beta-hairpin pocket contains more hydrophobic contacts and a network of bridging water molecules. In accord with these differences, we find that each CdiI protein only protects target bacteria from its cognate CdiA-CT toxin. The compact beta-hairpin binding pocket within the immunity protein represents a tractable system for the rationale design of small molecules to block CdiA-CT/CdiI complex formation. We synthesized a macrocyclic peptide mimic of the beta-hairpin from EC869 toxin and solved its structure in complex with cognate immunity protein. These latter studies suggest that small molecules could potentially be used to disrupt CDI toxin/immunity complexes.

Diversification of beta-Augmentation Interactions between CDI Toxin/Immunity Proteins.,Morse RP, Willett JL, Johnson PM, Zheng J, Credali A, Iniguez A, Nowick JS, Hayes CS, Goulding CW J Mol Biol. 2015 Nov 20;427(23):3766-84. doi: 10.1016/j.jmb.2015.09.020. Epub, 2015 Oct 9. PMID:26449640^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Morse RP, Willett JL, Johnson PM, Zheng J, Credali A, Iniguez A, Nowick JS, Hayes CS, Goulding CW. Diversification of beta-Augmentation Interactions between CDI Toxin/Immunity Proteins. J Mol Biol. 2015 Nov 20;427(23):3766-84. doi: 10.1016/j.jmb.2015.09.020. Epub, 2015 Oct 9. PMID:26449640 doi:http://dx.doi.org/10.1016/j.jmb.2015.09.020
↑ Morse RP, Willett JL, Johnson PM, Zheng J, Credali A, Iniguez A, Nowick JS, Hayes CS, Goulding CW. Diversification of beta-Augmentation Interactions between CDI Toxin/Immunity Proteins. J Mol Biol. 2015 Nov 20;427(23):3766-84. doi: 10.1016/j.jmb.2015.09.020. Epub, 2015 Oct 9. PMID:26449640 doi:http://dx.doi.org/10.1016/j.jmb.2015.09.020

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/4zqu"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4zqu]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Salmonella_enterica_subsp._enterica_serovar_Rubislaw_str._ATCC_10717 Salmonella enterica subsp. enterica serovar Rubislaw str. ATCC 10717] and [https://en.wikipedia.org/wiki/Yersinia_pseudotuberculosis_YPIII Yersinia pseudotuberculosis YPIII]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZQU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZQU FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.09&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=4zqu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zqu OCA], [https://pdbe.org/4zqu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zqu RCSB], [https://www.ebi.ac.uk/pdbsum/4zqu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zqu ProSAT]</span></td></tr>
 </table>

4zqu

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Current revision

CdiA-CT/CdiI toxin and immunity complex from Yersinia pseudotuberculosis

Structural highlights

Function

Publication Abstract from PubMed

References

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