TY - JOUR
T1 - Cooperative folding kinetics of BBL protein and peripheral subunit-binding domain homologues
AU - Yu, Wookyung
AU - Chung, Kwanghoon
AU - Cheon, Mookyung
AU - Heo, Muyoung
AU - Han, Kyou Hoon
AU - Ham, Sihyun
AU - Chang, Iksoo
PY - 2008/2/19
Y1 - 2008/2/19
N2 - 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.
AB - 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.
KW - Global downhill folding
KW - Protein folding mechanism
KW - Protein thermodynamics
KW - Relaxation kinetics of protein
UR - http://www.scopus.com/inward/record.url?scp=40649105020&partnerID=8YFLogxK
U2 - 10.1073/pnas.0708480105
DO - 10.1073/pnas.0708480105
M3 - Article
C2 - 18272497
AN - SCOPUS:40649105020
SN - 0027-8424
VL - 105
SP - 2397
EP - 2402
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 7
ER -