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J Am Chem Soc. 2015 Mar 18;137(10):3540-6. doi: 10.1021/ja5119368. Epub 2015 Mar 9.

Dynamics of equilibrium folding and unfolding transitions of titin immunoglobulin domain under constant forces.

Author information

1
†Department of Physics, Xiamen University, Xiamen, Fujian 361005, China.
2
‡Mechanobiology Institute, National University of Singapore, Singapore 117411.
3
¶Department of Biological Sciences, Columbia University, New York, New York 10027, United States.
4
§Department of Physics, National University of Singapore, Singapore 117542.
5
∥Centre for Bioimaging Sciences, National University of Singapore, Singapore 117546.

Abstract

The mechanical stability of force-bearing proteins is crucial for their functions. However, slow transition rates of complex protein domains have made it challenging to investigate their equilibrium force-dependent structural transitions. Using ultra stable magnetic tweezers, we report the first equilibrium single-molecule force manipulation study of the classic titin I27 immunoglobulin domain. We found that individual I27 in a tandem repeat unfold/fold independently. We obtained the force-dependent free energy difference between unfolded and folded I27 and determined the critical force (∼5.4 pN) at which unfolding and folding have equal probability. We also determined the force-dependent free energy landscape of unfolding/folding transitions based on measurement of the free energy cost of unfolding. In addition to providing insights into the force-dependent structural transitions of titin I27, our results suggest that the conformations of titin immunoglobulin domains can be significantly altered during low force, long duration muscle stretching.

PMID:
25726700
PMCID:
PMC4446711
DOI:
10.1021/ja5119368
[Indexed for MEDLINE]
Free PMC Article

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