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Friday, 28 October, 2011

The Complex Folding Network of Single Calmodulin Molecules

J. Stigler, F. Ziegler, A. Gieseke, J. C. M. Gebhardt, M. Rief -
Science, Vol. 334, no. 6055, pp. 512-516 (2011)

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.


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