Hidden complexity in the isomerization dynamics of Holliday junctions

作者：Hyeon Changbong^*; Lee Jinwoo; Yoon Jeseong; Hohng Sungchul; Thirumalai D

来源：Nature Chemistry, 2012, 4(11): 907-914.

DOI：10.1038/NCHEM.1463

A plausible consequence of the rugged folding energy landscapes inherent to biomolecules is that there may be more than one functionally competent folded state. Indeed, molecule-to-molecule variations in the folding dynamics of enzymes and ribozymes have recently been identified in single-molecule experiments, but without systematic quantification or an understanding of their structural origin. Here, using concepts from glass physics and complementary clustering analysis, we provide a quantitative method to analyse single-molecule fluorescence resonance energy transfer (smFRET) data, thereby probing the isomerization dynamics of Holliday junctions, which display such heterogeneous dynamics over a long observation time (T-obs approximate to 40 s). We show that the ergodicity of Holliday junction dynamics is effectively broken and that their conformational space is partitioned into a folding network of kinetically disconnected clusters. Theory suggests that the persistent heterogeneity of Holliday junction dynamics is a consequence of internal multiloops with varying sizes and flexibilities frozen by Mg2+ ions. An annealing experiment using Mg2+ pulses lends support to this idea by explicitly showing that interconversions between trajectories with different patterns can be induced.

• 出版日期2012-11