The application of direct force to a protein enables to probe wide regions of its energy surface through conformational transitions as unfolding, extending, recoiling, collapsing, and refolding. While unfolding under force typically displayed a two-state behavior, refolding under force, from highly extended unfolded states, displayed a more complex behavior. The first recording of protein refolding at a force quench step displayed an initial rapid elastic recoil, followed by a plateau phase at some extension, concluding with a collapse to a final state, at which refolding occurred. These findings stirred a lively discussion, which led to further experimental and theoretical investigation of this behavior. It was demonstrated that the polymeric chain of the unfolded protein is required to fully collapse to a globular conformation for the maturation of native structure. This behavior was modeled using one-dimensional free energy landscape over the end-to-end length reaction coordinate, the collective measured variable. However, at low forces, conformational space is not well captured by such models, and using two-dimensional energy surfaces provides further insight into the dynamics of this process. This work reviews the main concepts of protein refolding under constant force, which is essential for understanding how mechanotransducing proteins operate in vivo.
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Cover Image
Cover Image
The image represents talin in focal adhesions. Talin is a mechanosensitive molecule that connects the integrin receptors in the cell membrane with the cytoskeleton. It is exposed to mechanical stretching, which induces the unfolding of its structure. This controls talin's interaction with other proteins, such as Deleted in Liver Cancer (DLC), which is a tumour suppressor and negative regulator of cell contractility. To learn more about this, please see the articles in this issue by Burridge (pages 673–675), Barnett and Kanchanawong (pages 677–680), and Popa and Berkovich (pages 687–699). The image was prepared by Magdalena von Essen, background picture: Vesa Hytönen.
Mechanobiology: protein refolding under force
Armando del Río Hernández, Ionel Popa, Ronen Berkovich; Mechanobiology: protein refolding under force. Emerg Top Life Sci 21 December 2018; 2 (5): 687–699. doi: https://doi.org/10.1042/ETLS20180044
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