title: A PDZ domain recapitulates a unifying mechanism for protein folding.
abstract: A unifying view has been recently proposed according to which the classical diffusion-collision and nucleation-condensation models may represent two extreme manifestations of an underlying common mechanism for the folding of small globular proteins. We report here the characterization of the folding process of the PDZ domain, a protein that recapitulates the three canonical steps involved in this unifying mechanism, namely: (i) the early formation of a weak nucleus that determines the native-like topology of a large portion of the structure, (ii) a global collapse of the entire polypeptide chain, and (iii) the consolidation of the remaining partially structured regions to achieve the native state conformation. These steps, which are clearly detectable in the PDZ domain investigated here, may be difficult to distinguish experimentally in other proteins, which would thus appear to follow one of the two limiting mechanisms. The analysis of the (un)folding kinetics for other three-state proteins (when available) appears consistent with the predictions ensuing from this unifying mechanism, thus providing a powerful validation of its general nature.
authors.affiliation: Istituto Pasteur-Fondazione Cenci Bolognetti e Istituto di Biologia e Patologia Molecolari del CNR, Dipartimento di Scienze Biochimiche "A. Rossi Fanelli," Università di Roma "La Sapienza," Piazzale A. Moro 5, 00185 Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Gianni
authors.forename: Christian D
authors.initials: CD
authors.lastname: Geierhaas
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Calosci
authors.forename: Per
authors.initials: P
authors.lastname: Jemth
authors.forename: Geerten W
authors.initials: GW
authors.lastname: Vuister
authors.forename: Carlo
authors.initials: C
authors.lastname: Travaglini-Allocatelli
authors.forename: Michele
authors.initials: M
authors.lastname: Vendruscolo
authors.forename: Maurizio
authors.initials: M
authors.lastname: Brunori
mesh_terms: D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013816:Thermodynamics