Open AccessCooperative folding kinetics of BBL protein and peripheral subunit-binding domain homologues
Author(s) -
Wookyung Yu,
Kyu-Hyuck Chung,
Mookyung Cheon,
Muyoung Heo,
KyouHoon Han,
Sihyun Ham,
Iksoo Chang
Publication year - 2008
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0708480105
Subject(s) - downhill folding , protein folding , energy landscape , folding (dsp implementation) , kinetics , contact order , phi value analysis , chemistry , folding funnel , biophysics , relaxation (psychology) , physics , statistical physics , thermodynamics , biology , biochemistry , neuroscience , quantum mechanics , electrical engineering , engineering
Recent experiments claiming that Naf-BBL protein follows a global downhill folding raised an important controversy as to the folding mechanism of fast-folding proteins. Under the global downhill folding scenario, not only do proteins undergo a gradual folding, but folding events along the continuous folding pathway also could be mapped out from the equilibrium denaturation experiment. Based on the exact calculation using a free energy landscape, relaxation eigenmodes from a master equation, and Monte Carlo simulation of an extended Muñoz–Eaton model that incorporates multiscale-heterogeneous pairwise interactions between amino acids, here we show that the very nature of a two-state cooperative transition such as a bimodal distribution from an exact free energy landscape and biphasic relaxation kinetics manifest in the thermodynamics and folding–unfolding kinetics of BBL and peripheral subunit-binding domain homologues. Our results provide an unequivocal resolution to the fundamental controversy related to the global downhill folding scheme, whose applicability to other proteins should be critically reexamined.