title: Unfolding of heptameric co-chaperonin protein follows "fly casting" mechanism: observation of transient nonnative heptamer.
abstract: Protein recognition and binding play a fundamental role in living systems but sometimes also result in pathological aggregates. To probe the coupling between folding and binding in a homoheptameric system, we have characterized the time-resolved unfolding/disassembly mechanism of human co-chaperonin protein 10 (cpn10) by a combination of experimental and computational methods. The results from both approaches are in excellent agreement and make obvious that the kinetic process is three-state: an initial polypeptide-unfolding step, resulting in a non-native heptamer, is followed by a slower heptamer-dissociation step. This demonstrates that the barriers on the kinetic free-energy landscape are defined by thermodynamic stability. cpn10 is one of few, and the only heptameric, experimentally characterized system that follows the "fly casting scenario" of molecular recognition.
authors.affiliation: Department of Chemistry, Rice University, Houston, Texas 77030, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Perham
authors.forename: Mingzhi
authors.initials: M
authors.lastname: Chen
authors.forename: Jianpeng
authors.initials: J
authors.lastname: Ma
authors.forename: Pernilla
authors.initials: P
authors.lastname: Wittung-Stafshede
mesh_terms: D018835:Chaperonin 10 / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D017510:Protein Folding; D017433:Protein Structure, Secondary; D013050:Spectrometry, Fluorescence
chemical_list: D018835:Chaperonin 10