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

Nerita 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....

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Autores principales: Esperante, Sebastián A., Covaleda, Giovanni, Trejo, Sebastián Alejandro, Bronsoms, Silvia, Aviles, Francesc X., Ventura, Salvador
Formato: Articulo
Lenguaje:Inglés
Publicado: 2017
Materias:
Bioquímica
Nerita Versicolor
Inhibitor
Disulfides
Protein Folding
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/87177
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-87177
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Bioquímica
Nerita Versicolor
Inhibitor
Disulfides
Protein Folding
spellingShingle Bioquímica
Nerita Versicolor
Inhibitor
Disulfides
Protein Folding
Esperante, Sebastián A.
Covaleda, Giovanni
Trejo, Sebastián Alejandro
Bronsoms, Silvia
Aviles, Francesc X.
Ventura, Salvador
Plasticity in the Oxidative Folding Pathway of the High Affinity Nerita Versicolor Carboxypeptidase Inhibitor (NvCI)
topic_facet Bioquímica
Nerita Versicolor
Inhibitor
Disulfides
Protein Folding
description Nerita 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.
format Articulo
Articulo
author Esperante, Sebastián A.
Covaleda, Giovanni
Trejo, Sebastián Alejandro
Bronsoms, Silvia
Aviles, Francesc X.
Ventura, Salvador
author_facet Esperante, Sebastián A.
Covaleda, Giovanni
Trejo, Sebastián Alejandro
Bronsoms, Silvia
Aviles, Francesc X.
Ventura, Salvador
author_sort Esperante, Sebastián A.
title Plasticity in the Oxidative Folding Pathway of the High Affinity Nerita Versicolor Carboxypeptidase Inhibitor (NvCI)
title_short Plasticity in the Oxidative Folding Pathway of the High Affinity Nerita Versicolor Carboxypeptidase Inhibitor (NvCI)
title_full Plasticity in the Oxidative Folding Pathway of the High Affinity Nerita Versicolor Carboxypeptidase Inhibitor (NvCI)
title_fullStr Plasticity in the Oxidative Folding Pathway of the High Affinity Nerita Versicolor Carboxypeptidase Inhibitor (NvCI)
title_full_unstemmed Plasticity in the Oxidative Folding Pathway of the High Affinity Nerita Versicolor Carboxypeptidase Inhibitor (NvCI)
title_sort plasticity in the oxidative folding pathway of the high affinity nerita versicolor carboxypeptidase inhibitor (nvci)
publishDate 2017
url http://sedici.unlp.edu.ar/handle/10915/87177
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bdutipo_str Repositorios
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