A localized specific interaction alters the unfolding pathways of structural homologues

Détails

ID Serval
serval:BIB_5D93AFD25133
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
A localized specific interaction alters the unfolding pathways of structural homologues
Périodique
Journal of the American Chemical Society
Auteur(s)
Xu  G., Narayan  M., Kurinov  I., Ripoll  D. R., Welker  E., Khalili  M., Ealick  S. E., Scheraga  H. A.
ISSN
0002-7863 (Print)
Statut éditorial
Publié
Date de publication
02/2006
Volume
128
Numéro
4
Pages
1204-13
Notes
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S. --- Old month value: Feb 1
Résumé
Reductive unfolding studies of proteins are designed to provide information about intramolecular interactions that govern the formation (and stabilization) of the native state and about folding/unfolding pathways. By mutating Tyr92 to G, A, or L in the model protein, bovine pancreatic ribonuclease A, and through analysis of temperature factors and molecular dynamics simulations of the crystal structures of these mutants, it is demonstrated that the markedly different reductive unfolding rates and pathways of ribonuclease A and its structural homologue onconase can be attributed to a single, localized, ring-stacking interaction between Tyr92 and Pro93 in the bovine variant. The fortuitous location of this specific stabilizing interaction in a disulfide-bond-containing loop region of ribonuclease A results in the localized modulation of protein dynamics that, in turn, enhances the susceptibility of the disulfide bond to reduction leading to an alteration in the reductive unfolding behavior of the homologues. These results have important implications for folding studies involving topological determinants to obtain folding/unfolding rates and pathways, for protein structure-function prediction through fold recognition, and for predicting proteolytic cleavage sites.
Mots-clé
Animals Cattle Models, Molecular Mutagenesis, Site-Directed Oxidation-Reduction Protein Conformation Protein Folding Recombinant Proteins/chemistry/genetics/metabolism Ribonuclease, Pancreatic/*chemistry/genetics/metabolism Ribonucleases/*chemistry/genetics/metabolism Thermodynamics
Pubmed
Web of science
Création de la notice
24/01/2008 14:41
Dernière modification de la notice
20/08/2019 14:15
Données d'usage