Title

NMR spectroscopy of 14-3-3zeta reveals a flexible C-terminal extension: differentiation of the chaperone and phosphoserine-binding activities of 14-3-3zeta

RIS ID

38051

Publication Details

Williams, D. M., Ecroyd, H., Goodwin, K. L., Dai, H., Fu, H., Woodcock, J. M., Zhang, L. & Carver, J. A. (2011). NMR spectroscopy of 14-3-3zeta reveals a flexible C-terminal extension: differentiation of the chaperone and phosphoserine-binding activities of 14-3-3zeta. Biochemical Journal, 437 (3), 493-503.

Abstract

Intracellular 14-3-3 proteins bind to many proteins, via a specific phosphoserine motif, regulating diverse cellular tasks including cell signalling and disease progression. The 14-3-3 isoform is a molecular chaperone, preventing the stressinduced aggregation of target proteins in a manner comparable with that of the unrelated sHsps (small heat-shock proteins). 1H-NMR spectroscopy revealed the presence of a flexible and unstructured C-terminal extension, 12 amino acids in length, which protrudes from the domain core of 14-3-3 and is similar in structure and length to the C-terminal extension of mammalian sHsps. The extension stabilizes 14-3-3, but has no direct role in chaperone action. Lys 49 is an important functional residue within the ligand-binding groove of 14-3-3 with K49E 14-3-3 exhibiting markedly reduced binding to phosphorylated and non-phosphorylated ligands. The R18 peptide binds to the binding groove of 14-3-3 with high affinity and also reduces the interaction of 14-3-3 ligands. However, neither the K49E mutation nor the presence of the R18 peptide affected the chaperone activity of 14-3-3, implying that the C-terminal extension and binding groove of 14-3-3 do not mediate interaction with target proteins during chaperone action. Other region(s) in 14-3-3 are most likely to be involved, i.e. the protein's chaperone and phosphoserine-binding activities are functionally and structurally separated. C The Authors Journal compilation C 2011 Biochemical Society.

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Link to publisher version (DOI)

http://dx.doi.org/10.1042/BJ20102178