The Complex Folding Network of Single Calmodulin Molecules.
Stigler, Johannes 1; Ziegler, Fabian 1; Gieseke, Anja 1; Gebhardt, Christof J. M. 1*; Rief, Matthias 1,2+
[Report] Science. 334(6055):512-516, October 28, 2011.

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: Direct observation of the detailed conformational fluctuations of a single protein molecule en route to its folded state has so far been realized only in silico. We have used single-molecule force spectroscopy to study the folding transitions of single calmodulin molecules. High-resolution optical tweezers assays in combination with hidden Markov analysis reveal a complex network of on- and off-pathway intermediates. Cooperative and anticooperative interactions across domain boundaries can be observed directly. The folding network involves four intermediates. Two off-pathway intermediates exhibit non-native interdomain interactions and compete with the ultrafast productive folding pathway.

Copyright (C) 2011 by the American Association for the Advancement of Science