期刊
BIOCHEMICAL JOURNAL
卷 437, 期 -, 页码 493-503出版社
PORTLAND PRESS LTD
DOI: 10.1042/BJ20102178
关键词
biophysical characterization; C-terminal flexibility; molecular chaperone; 14-3-3 protein; protein aggregation; protein-protein interaction
资金
- China Important National Science and Technology Specific Projects [2008ZX09401-05]
- Australian Research Council
- Australian National Health and Medical Research Council
- Australian Postgraduate Award
- Daphne Elliott Bursary
- AUGC/RC Heddle Award
- George Murray Scholarship
- Australian Bicentennial Scholarship
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 zeta isoform is a molecular chaperone, preventing the stress-induced aggregation of target proteins in a manner comparable with that of the unrelated sHsps (small heat-shock proteins). (1)H-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 zeta and is similar in structure and length to the C-terminal extension of mammalian sHsps. The extension stabilizes 14-3-3 zeta but has no direct role in chaperone action. Lys(49) is an important functional residue within the ligand-binding groove of 14-3-3 zeta with K49E 14-3-3 zeta exhibiting markedly reduced binding to phosphorylated and non-phosphorylated ligands. The R18 peptide binds to the binding groove of 14-3-3 zeta with high affinity and also reduces the interaction of 14-3-3 zeta ligands. However, neither the K49E mutation nor the presence of the R18 peptide affected the chaperone activity of 14-3-3 zeta implying that the C-terminal extension and binding groove of 14-3-3 zeta do not mediate interaction with target proteins during chaperone action. Other region(s) in 14-3-3 zeta are most likely to be involved, i.e. the protein's chaperone and phosphoserine-binding activities are functionally and structurally separated.
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