Elasticity of the Transition State Leading to an Unexpected Mechanical Stabilization of Titin Immunoglobulin Domains

Angewandte Chemie - International Edition

5 years ago

Elasticity of the Transition State Leading to an Unexpected Mechanical Stabilization of Titin Immunoglobulin Domains

Jie Yan, Guohua Yuan, Shimin Le, Mingxi Yao, Hu Chen, Hui Qian, Xin Zhou

The giant protein titin plays a critical role in regulating the passive elasticity of muscles, mainly through the stochastic unfolding and refolding of its numerous immunoglobulin domains in the I-band of sarcomeres. The unfolding dynamics of titin immunoglobulin domains at a force range greater than 100 pN has been studied by atomic force microscopy, while that at smaller physiological forces has not been measured before. By using magnetic tweezers, it is found that the titin I27 domain unfolds in a surprising non-monotonic force-dependent manner at forces smaller than 100 pN, with the slowest unfolding rate occurring around 22 pN. We further demonstrate that a model with single unfolding pathway taking into account the elasticity of the transition state can reproduce the experimental results. These results provide important novel insights into the regulation mechanism of the passive elasticity of muscle tissues. A catch bond is observed in mechanical protein unfolding. The titin immunoglobulin domain I27 unfolds slower under a stretching force when the force is smaller than 20 pN. The entropic elasticity of the transition state plays a role in a new mechanism to understand this catch-bond behavior.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/anie.201700411