4p5h: Difference between revisions
New page: '''Unreleased structure''' The entry 4p5h is ON HOLD Authors: Naylor, C.E., Yelland, T.S., Basak, A.K. Description: Structure of Clostridium perfringens Enterotoxin with a peptide deri... |
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==Structure of Clostridium perfringens Enterotoxin with a peptide derived from a modified version of ECL-2 of Claudin 2== | |||
<StructureSection load='4p5h' size='340' side='right'caption='[[4p5h]], [[Resolution|resolution]] 3.38Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4p5h]] is a 30 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridium_perfringens Clostridium perfringens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3zj3 3zj3]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4P5H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4P5H 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]] 3.38Å</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=4p5h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p5h OCA], [https://pdbe.org/4p5h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4p5h RCSB], [https://www.ebi.ac.uk/pdbsum/4p5h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4p5h ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CLD2_MOUSE CLD2_MOUSE] Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.<ref>PMID:10508613</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
CPE (Clostridium perfringens enterotoxin) is the major virulence determinant for C. perfringens type A food poisoning, the second most common bacterial food-borne illness in the UK and USA. After binding to its receptors, which include particular human claudins, the toxin forms pores in the cell membrane. The mature pore apparently contains a hexamer of CPE, claudin and, possibly, occludin. The combination of high binding specificity with cytotoxicity has resulted in CPE being investigated, with some success, as a targeted cytotoxic agent for oncotherapy. In this paper, we present the X-ray crystallographic structure of CPE in complex with a peptide derived from extracellular loop 2 of a modified, CPE binding Claudin-2, together with high-resolution native and pore-formation mutant structures. Our structure provides the first atomic resolution data on any part of a claudin molecule and reveals that claudin's CPE binding fingerprint (NPLVP), is in a tight turn conformation and binds, as expected, in CPE's C-terminal claudin binding groove. The leucine and valine residues insert into the binding groove while the first residue, asparagine, tethers the peptide via an interaction with CPE's aspartate 225 and the two prolines are required to maintain the tight turn conformation. Understanding the structural basis of the contribution these residues make to binding will aid in engineering CPE to target tumour cells. | |||
Structure of a C. perfringens Enterotoxin mutant in Complex with a Modified Claudin-2 Extracellular Loop 2.,Yelland TS, Naylor CE, Bagoban T, Savva CG, Moss DS, McClane BA, Blasig IE, Popoff M, Basak AK J Mol Biol. 2014 Jul 11. pii: S0022-2836(14)00329-5. doi:, 10.1016/j.jmb.2014.07.001. PMID:25020226<ref>PMID:25020226</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4p5h" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Clostridium perfringens]] | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | |||
[[Category: Basak AK]] | |||
[[Category: Naylor CE]] | |||
[[Category: Yelland TS]] | |||
Latest revision as of 10:11, 27 September 2023
Structure of Clostridium perfringens Enterotoxin with a peptide derived from a modified version of ECL-2 of Claudin 2Structure of Clostridium perfringens Enterotoxin with a peptide derived from a modified version of ECL-2 of Claudin 2
Structural highlights
FunctionCLD2_MOUSE Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.[1] Publication Abstract from PubMedCPE (Clostridium perfringens enterotoxin) is the major virulence determinant for C. perfringens type A food poisoning, the second most common bacterial food-borne illness in the UK and USA. After binding to its receptors, which include particular human claudins, the toxin forms pores in the cell membrane. The mature pore apparently contains a hexamer of CPE, claudin and, possibly, occludin. The combination of high binding specificity with cytotoxicity has resulted in CPE being investigated, with some success, as a targeted cytotoxic agent for oncotherapy. In this paper, we present the X-ray crystallographic structure of CPE in complex with a peptide derived from extracellular loop 2 of a modified, CPE binding Claudin-2, together with high-resolution native and pore-formation mutant structures. Our structure provides the first atomic resolution data on any part of a claudin molecule and reveals that claudin's CPE binding fingerprint (NPLVP), is in a tight turn conformation and binds, as expected, in CPE's C-terminal claudin binding groove. The leucine and valine residues insert into the binding groove while the first residue, asparagine, tethers the peptide via an interaction with CPE's aspartate 225 and the two prolines are required to maintain the tight turn conformation. Understanding the structural basis of the contribution these residues make to binding will aid in engineering CPE to target tumour cells. Structure of a C. perfringens Enterotoxin mutant in Complex with a Modified Claudin-2 Extracellular Loop 2.,Yelland TS, Naylor CE, Bagoban T, Savva CG, Moss DS, McClane BA, Blasig IE, Popoff M, Basak AK J Mol Biol. 2014 Jul 11. pii: S0022-2836(14)00329-5. doi:, 10.1016/j.jmb.2014.07.001. PMID:25020226[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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