A biosensor-based framework to measure latent proteostasis capacity

RJ Wood; AR Ormsby; M Radwan; D Cox; A Sharma; T Vöpel; S Ebbinghaus; M Oliveberg; GE Reid; A Dickson; DM Hatters

Journal article

A biosensor-based framework to measure latent proteostasis capacity

RJ Wood, AR Ormsby, M Radwan, D Cox, A Sharma, T Vöpel, S Ebbinghaus, M Oliveberg, GE Reid, A Dickson, DM Hatters

Nature Communications | NATURE PUBLISHING GROUP | Published : 2018

DOI: 10.1038/s41467-017-02562-5

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Abstract

The pool of quality control proteins (QC) that maintains protein-folding homeostasis (proteostasis) is dynamic but can become depleted in human disease. A challenge has been in quantitatively defining the depth of the QC pool. With a new biosensor, flow cytometry-based methods and mathematical modeling we measure the QC capacity to act as holdases and suppress biosensor aggregation. The biosensor system comprises a series of barnase kernels with differing folding stability that engage primarily with HSP70 and HSP90 family proteins. Conditions of proteostasis stimulation and stress alter QC holdase activity and aggregation rates. The method reveals the HSP70 chaperone cycle to be rate limited..

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University of Melbourne Researchers

Gavin Reid Author

Danny M Hatters Author

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Grants

Awarded by National Science Foundation

Funding Acknowledgements

This work was funded by grants from the Australian Research Council Future Fellowships scheme FT120100039 (D.M.H.), and National Health and Medical Research Council Project grants APP1049458 (D.M.H.) and APP1049459 (D.M.H.), and Human Frontier Science Program research grant RGP0022/2017 (D.M.H, S.E. and A.D.). S.E. acknowledges funding from the Cluster of Excellence RESOLV (EXC 1069) funded by the German Research Foundation (D.F.G.).