Plasticity in the Oxidative Folding Pathway of the High Affinity Nerita Versicolor Carboxypeptidase Inhibitor (NvCI)

dc.creatorEsperante, Sebastián A.
dc.creatorCovaleda, Giovanni
dc.creatorTrejo, Sebastián Alejandro
dc.creatorBronsoms, Silvia
dc.creatorAviles, Francesc X.
dc.creatorVentura, Salvador
dc.date2017
dc.date2019-12-10T17:38:53Z
dc.date.accessioned2023-07-14T17:40:43Z
dc.date.available2023-07-14T17:40:43Z
dc.identifierhttp://sedici.unlp.edu.ar/handle/10915/87177
dc.identifierissn:2045-2322
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/7428414
dc.descriptionNerita Versicolor carboxypeptidase inhibitor (NvCI) is the strongest inhibitor reported so far for the M14A subfamily of carboxypeptidases. It comprises 53 residues and a protein fold composed of a two-stranded antiparallel β sheet connected by three loops and stabilized by three disulfide bridges. Here we report the oxidative folding and reductive unfolding pathways of NvCI. Much debate has gone on whether protein conformational folding guides disulfide bond formation or instead they are disulfide bonds that favour the arrangement of local or global structural elements. We show here that for NvCI both possibilities apply. Under physiological conditions, this protein folds trough a funnelled pathway involving a network of kinetically connected native-like intermediates, all sharing the disulfide bond connecting the two β-strands. In contrast, under denaturing conditions, the folding of NvCI is under thermodynamic control and follows a "trial and error" mechanism, in which an initial quasi-stochastic population of intermediates rearrange their disulfide bonds to attain the stable native topology. Despite their striking mechanistic differences, the efficiency of both folding routes is similar. The present study illustrates thus a surprising plasticity in the folding of this extremely stable small disulfide-rich inhibitor and provides the basis for its redesign for biomedical applications.
dc.descriptionInstituto Multidisciplinario de Biología Celular
dc.formatapplication/pdf
dc.languageen
dc.rightshttp://creativecommons.org/licenses/by/4.0/
dc.rightsCreative Commons Attribution 4.0 International (CC BY 4.0)
dc.subjectBioquímica
dc.subjectNerita Versicolor
dc.subjectInhibitor
dc.subjectDisulfides
dc.subjectProtein Folding
dc.titlePlasticity in the Oxidative Folding Pathway of the High Affinity Nerita Versicolor Carboxypeptidase Inhibitor (NvCI)
dc.typeArticulo
dc.typeArticulo


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