Hidden complexity in the isomerization dynamics of Holliday junctions
Author: ["Changbong Hyeon","Jinwoo Lee","Jeseong Yoon","Sungchul Hohng","D. Thirumalai"]
Publication: Nature Chemistry
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Abstract
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 (Tobs ≈ 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. Single-molecule experiments reveal substantial molecule-to-molecule variation in the Mg2+-induced isomerization dynamics of Holliday junctions (HJs). Effective ergodicity breaking of time trajectories results in the partitioning of HJ dynamics into multiple clusters. The observed dynamical heterogeneity is a consequence of various internal multiloop conformations that are frozen by Mg2+ ions.
Cite this article
Hyeon, C., Lee, J., Yoon, J. et al. Hidden complexity in the isomerization dynamics of Holliday junctions. Nature Chem 4, 907–914 (2012). https://doi.org/10.1038/nchem.1463
