한빛사 논문
Tae Wu Kima,b,c, Sang Jin Leea,b,c, Junbeom Joa,b,c, Jong Goo Kima,b,c, Hosung Kia,b,c, Chang Woo Kima, Kwang Hyun Choa, Jungkweon Choic, Jae Hyuk Leed, Michael Wulffe, Young Min Rheea,1, and Hyotcherl Iheea,b,c,1
aDepartment of Chemistry, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea; bKI for the BioCentury, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea; cCenter for Nanomaterials and Chemical Reactions, Institute for Basic Science, Daejeon 34141, Republic of Korea; dXFEL Beamline Department, Pohang Accelerator Laboratory, Pohang 37673, Republic of Korea; and eExperiments Division, European Synchrotron Radiation Facility, F-38043 Grenoble Cedex, France
1To whom correspondence may be addressed.
Abstract
One of the most challenging tasks in biological science is to understand how a protein folds. In theoretical studies, the hypothesis adopting a funnel-like free-energy landscape has been recognized as a prominent scheme for explaining protein folding in views of both internal energy and conformational heterogeneity of a protein. Despite numerous experimental efforts, however, comprehensively studying protein folding with respect to its global conformational changes in conjunction with the heterogeneity has been elusive. Here we investigate the redox-coupled folding dynamics of equine heart cytochrome c (cyt-c) induced by external electron injection by using time-resolved X-ray solution scattering. A systematic kinetic analysis unveils a kinetic model for its folding with a stretched exponential behavior during the transition toward the folded state. With the aid of the ensemble optimization method combined with molecular dynamics simulations, we found that during the folding the heterogeneously populated ensemble of the unfolded state is converted to a narrowly populated ensemble of folded conformations. These observations obtained from the kinetic and the structural analyses of X-ray scattering data reveal that the folding dynamics of cyt-c accompanies many parallel pathways associated with the heterogeneously populated ensemble of unfolded conformations, resulting in the stretched exponential kinetics at room temperature. This finding provides direct evidence with a view to microscopic protein conformations that the cyt-c folding initiates from a highly heterogeneous unfolded state, passes through still diverse intermediate structures, and reaches structural homogeneity by arriving at the folded state.
protein folding, cytochrome c, time-resolved X-ray scattering, ensemble, molecular dynamics simulation
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TOP52020년 후보
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