Does protein unfolding play a functional role in vivo?
- PMID: 32761965
- DOI: 10.1111/febs.15508
Does protein unfolding play a functional role in vivo?
Abstract
Unfolding and refolding of multidomain proteins under force have yet to be recognized as a major mechanism of function for proteins in vivo. In this review, we discuss the inherent properties of multidomain proteins under a force vector from a structural and functional perspective. We then characterize three main systems where multidomain proteins could play major roles through mechanical unfolding: muscular contraction, cellular mechanotransduction, and bacterial adhesion. We analyze how key multidomain proteins for each system can produce a gain-of-function from the perspective of a fine-tuned quantized response, a molecular battery, delivery of mechanical work through refolding, elasticity tuning, protection and exposure of cryptic sites, and binding-induced mechanical changes. Understanding how mechanical unfolding and refolding affect function will have important implications in designing mechano-active drugs against conditions such as muscular dystrophy, cancer, or novel antibiotics.
Keywords: bacterial adhesion; cellular mechanotransduction; energy landscape; force spectroscopy; muscular contraction; protein unfolding.
© 2020 Federation of European Biochemical Societies.
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