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==Structural Plasticity of Paneth cell alpha-Defensins: Characterization of Salt-Bridge Deficient Analogues of Mouse Cryptdin-4== | |||
<StructureSection load='2lew' size='340' side='right'caption='[[2lew]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2lew]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LEW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LEW FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</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=2lew FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lew OCA], [https://pdbe.org/2lew PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2lew RCSB], [https://www.ebi.ac.uk/pdbsum/2lew PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2lew ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/DEFA4_MOUSE DEFA4_MOUSE] Probably contributes to the antimicrobial barrier function of the small bowel mucosa. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Salt-bridge interactions between acidic and basic amino acids contribute to the structural stability of proteins and to protein-protein interactions. A conserved salt-bridge is a canonical feature of the alpha-defensin antimicrobial peptide family, but the role of this common structural element has not been fully elucidated. We have investigated mouse Paneth cell alpha-defensin cryptdin-4 (Crp4) and peptide variants with mutations at Arg(7) or Glu(15) residue positions to disrupt the salt-bridge and assess the consequences on Crp4 structure, function, and stability. NMR analyses showed that both (R7G)-Crp4 and (E15G)-Crp4 adopt native-like structures, evidence of fold plasticity that allows peptides to reshuffle side chains and stabilize the structure in the absence of the salt-bridge. In contrast, introduction of a large hydrophobic side chain at position 15, as in (E15L)-Crp4 cannot be accommodated in the context of the Crp4 primary structure. Regardless of which side of the salt-bridge was mutated, salt-bridge variants retained bactericidal peptide activity with differential microbicidal effects against certain bacterial cell targets, confirming that the salt-bridge does not determine bactericidal activity per se. The increased structural flexibility induced by salt-bridge disruption enhanced peptide sensitivity to proteolysis. Although sensitivity to proteolysis by MMP7 was unaffected by most Arg(7) and Glu(15) substitutions, every salt-bridge variant was degraded extensively by trypsin. Moreover, the salt-bridge facilitates adoption of the characteristic alpha-defensin fold as shown by the impaired in vitro refolding of (E15D)-proCrp4, the most conservative salt-bridge disrupting replacement. In Crp4, therefore, the canonical alpha-defensin salt-bridge facilitates adoption of the characteristic alpha-defensin fold, which decreases structural flexibility and confers resistance to degradation by proteinases. | |||
The alpha-defensin salt-bridge induces backbone stability to facilitate folding and confer proteolytic resistance.,Andersson HS, Figueredo SM, Haugaard-Kedstrom LM, Bengtsson E, Daly NL, Qu X, Craik DJ, Ouellette AJ, Rosengren KJ Amino Acids. 2012 Jan 29. PMID:22286872<ref>PMID:22286872</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2lew" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Defensin 3D structures|Defensin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | |||
[[Category: Andersson HS]] | |||
[[Category: Bengtsson E]] | |||
[[Category: Craik DJ]] | |||
[[Category: Daly NL]] | |||
[[Category: Haugaard-Kedstrom LM]] | |||
[[Category: Rosengren K]] | |||