Moonlighting chaperone-like activity of the universal regulatory 14-3-3 proteinsстатья
Статья опубликована в высокорейтинговом журнале
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Дата последнего поиска статьи во внешних источниках: 30 августа 2017 г.
Аннотация:The ubiquitous eukaryotic 14-3-3 proteins coordinate multiple cellular processes due to their well-known regulatory function that is based on specific recognition of phosphorylated motifs in their partners. In this context, 14-3-3 proteins have, in reports, been called ’chaperones’. Although in the classical meaning this is not fully correct, recent studies have revealed that 14-3-3 can indeed be an integral part of the protein quality control system, as they: (i) display ATP-independent anti-aggregation (’holdase’) activity, similar to that of the unrelated small heat shock proteins; (ii) assist in clearing misfolded proteins by directing them to proteasomes or aggresomes; (iii) cooperate with classical chaperones for substrate refolding; and also (iv) are associated with neurodegenerative disorders by affecting aggregation of tau, prion protein, α-synuclein, and huntingtin, etc. Importantly, these activities are usually independent of substrate phosphorylation and therefore should be considered as a distinct, moonlighting, function of 14-3-3 proteins, that mimic and complement the functions of dedicated molecular chaperones. Although the precise mechanism of this activity is still unknown, it has been shown that it is not dependent on the unstructured C-terminal region or the amphipathic phosphopeptide-binding groove. However, since disassembly of 14-3-3 dimers significantly increases their chaperone-like activity, the dimer interface, located in the N-terminus of 14-3-3, possessing a high disorder propensity and pronounced hydrophobicity, is likely to be involved. Various factors affecting the oligomeric status of 14-3-3 can thus regulate the balance between regulatory phosphomotif binding and genuine chaperone-like activity. Understanding the latter mode of 14-3-3 functioning is fundamental to defining the underlying molecular mechanisms for a range of human disorders. This article is protected by copyright. All rights reserved.