Journal article
Metastability of native proteins and the phenomenon of amyloid formation
AJ Baldwin, TPJ Knowles, GG Tartaglia, AW Fitzpatrick, GL Devlin, SL Shammas, CA Waudby, MF Mossuto, S Meehan, SL Gras, J Christodoulou, SJ Anthony-Cahill, PD Barker, M Vendruscolo, CM Dobson
Journal of the American Chemical Society | Published : 2011
DOI: 10.1021/ja2017703
Abstract
An experimental determination of the thermodynamic stabilities of a series of amyloid fibrils reveals that this structural form is likely to be the most stable one that protein molecules can adopt even under physiological conditions. This result challenges the conventional assumption that functional forms of proteins correspond to the global minima in their free energy surfaces and suggests that living systems are conformationally as well as chemically metastable. © 2011 American Chemical Society.
Grants
Awarded by Medical Research Council
Funding Acknowledgements
We thank Wilhelm Huck, Maarten Biesheuvel, David Chandler, and David Bowler for helpful discussions. This work was supported by the EPSRC, BBSRC, EMBO (A.J.B.), St John's College, Cambridge (T.P.J.K), the Australian Academy of Science (S.L. G.), the Wellcome Trust (C.M.D.), and the Leverhulme Trust (M.V., C.M.D.).