Unfolding of heptameric co-chaperonin protein follows "fly casting" mechanism: observation of transient nonnative heptamer.
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.
Perham
Michael
M
Department of Chemistry, Rice University, Houston, Texas 77030, USA.
Chen
Mingzhi
M
Ma
Jianpeng
J
Wittung-Stafshede
Pernilla
P
D018835:Chaperonin 10 / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D017510:Protein Folding; D017433:Protein Structure, Secondary; D013050:Spectrometry, Fluorescence
D018835:Chaperonin 10