Biophysical approaches for the study of interactions between molecular chaperones and protein aggregates
Wright, Maya A
Royal Society of Chemistry
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Wright, M. A., Aprile, F., Arosio, P., Vendruscolo, M., Dobson, C., & Knowles, T. (2015). Biophysical approaches for the study of interactions between molecular chaperones and protein aggregates. Chemical Communications, 51 14425-14434. https://doi.org/10.1039/C5CC03689E
Molecular chaperones are key components of the arsenal of cellular defence mechanisms active against protein aggregation. In addition to their established role in assisting protein folding, there is increasing evidence that molecular chaperones are able to protect against a range of potentially damaging aspects of protein behaviour, including misfolding and aggregation events that can result in the generation of amyloid fibrils. These latter species are ordered aggregates whose formation is implicated in the onset and progression of neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. The interactions between molecular chaperones and different amyloidogenic protein species are difficult to study owing to the inherent heterogeneity of fibril forming systems as well as the dynamic nature of molecular chaperones under physiological conditions. As a consequence, understanding the detailed microscopic mechanisms underlying the nature and means of inhibition of aggregate growth remains challenging yet is a key objective for protein biophysics. In this review, we discuss recent results from biophysical studies on the interactions between molecular chaperones and protein aggregates. In particular, we focus on the insights gained from current experimental techniques into the dynamic self-assembly of these molecular inhibitors, and highlight the opportunity that future biophysical approaches have in advancing our understanding of the biological function of molecular chaperones.
We acknowledge financial support from the Frances and Augustus Newman Foundation (TPJK), the Biological Sciences Research Council (TPJK), the European Research Council (TPJK and MAW), the Wellcome Trust (CMD, TPJK and MV), and the Marie Curie fellowship scheme (PA).
External DOI: https://doi.org/10.1039/C5CC03689E
This record's URL: https://www.repository.cam.ac.uk/handle/1810/252440
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Licence URL: http://creativecommons.org/licenses/by/4.0/