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Effects of Evolutionary Distance on Protein Dynamics, Antibacterial Activity, and Cytotoxicity in Members of the Ribonuclease 3 Subfamily

Bernard, David N.; Létourneau, Myriam; Gagné, Donald; Groleau, Marie-Christine; Déziel, Éric; Doucet, Nicolas . Effects of Evolutionary Distance on Protein Dynamics, Antibacterial Activity, and Cytotoxicity in Members of the Ribonuclease 3 Subfamily In: 31st Annual Symposium of the Protein-Society, 24-27 juin 2017, Montréal (Québec) Canada.

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Résumé

Recent experimental evidence suggests that conformational exchange may affect catalytic function ina number of enzyme systems. However, the underlying mechanism(s) linking flexibility with biologicalfunction remains elusive. For instance, it is unknown whether protein sequence and/or structure areevolutionarily conserved to promote conformational exchange among functional enzyme homologs.Herein, we used a combination of functional assays and NMR relaxation experiments to characterizethe catalytically relevant millisecond time frame in various members of the pancreatic-like ribonucle-ase superfamily. To provide information on evolutionary conservation, dynamics, and biological func-tion, we characterized mammalian homologs of human ribonuclease 3 (also known as EosinophilCationic Protein, or ECP), specifically focusing on monkey ECP homologs from Macaca fascicularis,Pongo pygmaeus, Pongo abelii, and Aotus trivirgatus. Our findings show that conformationalexchange in the monkey enzymes strongly resembles that of their human counterpart, with subtlechanges in exchange rates and/or structural localization, thus providing insights into the effects ofsequence and phylogenetic diversity on protein dynamics. In parallel, antibacterial assays against E.coli and S. aureus illustrate that antimicrobial activity correlates with evolutionary distance from thecommon ancestor. Finally, cytotoxicity assays performed on HeLa cells highlight a stark difference inpotency between human ECP, monkey enzymes, and the prototypical RNase A homolog. Altogether,these experiments provide further details on the potential interdependence between protein functionand atomic-scale flexibility.

Type de document: Document issu d'une conférence ou d'un atelier
Informations complémentaires: Protein Science (2017), 26 (S1), 78. Affiche scientifique: POS230
Mots-clés libres: -
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 05 août 2019 20:44
Dernière modification: 05 août 2019 20:44
URI: http://espace.inrs.ca/id/eprint/8086

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