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 14-3-3ζ 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). 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 14-3-3ζ and is similar in structure and length to the C-terminal extension of mammalian sHsps. The extension stabilizes 14-3-3ζ, but has no direct role in chaperone action. Lys49 is an important functional residue within the ligand-binding groove of 14-3-3ζ with K49E 14-3-3ζ exhibiting markedly reduced binding to phosphorylated and non-phosphorylated ligands. The R18 peptide binds to the binding groove of 14-3-3ζ with high affinity and also reduces the interaction of 14-3-3ζ ligands. However, neither the K49E mutation nor the presence of the R18 peptide affected the chaperone activity of 14-3-3ζ, implying that the C-terminal extension and binding groove of 14-3-3ζ do not mediate interaction with target proteins during chaperone action. Other region(s) in 14-3-3ζ 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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Research Article|
July 13 2011
NMR spectroscopy of 14-3-3ζ reveals a flexible C-terminal extension: differentiation of the chaperone and phosphoserine-binding activities of 14-3-3ζ
Danielle M. Williams;
Danielle M. Williams
*School of Chemistry and Physics, The University of Adelaide, Adelaide, SA 5005, Australia
†Centre for Cancer Biology, SA Pathology, Adelaide, SA 5000, Australia
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Heath Ecroyd;
Heath Ecroyd
*School of Chemistry and Physics, The University of Adelaide, Adelaide, SA 5005, Australia
‡School of Biological Sciences, University of Wollongong, NSW 2522, Australia
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Katy L. Goodwin;
Katy L. Goodwin
*School of Chemistry and Physics, The University of Adelaide, Adelaide, SA 5005, Australia
†Centre for Cancer Biology, SA Pathology, Adelaide, SA 5000, Australia
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Huanqin Dai;
Huanqin Dai
§Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100190, China
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Haian Fu;
Haian Fu
∥Department of Pharmacology and Emory Chemical Biology Discovery Center, Emory University, Atlanta, GA 30322, U.S.A.
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Joanna M. Woodcock;
Joanna M. Woodcock
†Centre for Cancer Biology, SA Pathology, Adelaide, SA 5000, Australia
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Lixin Zhang;
Lixin Zhang
1
§Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100190, China
1Correspondence may be addressed to either of these authors (email lzhang03@gmail.com or john.carver@adelaide.edu.au).
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John A. Carver
John A. Carver
1
*School of Chemistry and Physics, The University of Adelaide, Adelaide, SA 5005, Australia
1Correspondence may be addressed to either of these authors (email lzhang03@gmail.com or john.carver@adelaide.edu.au).
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Publisher: Portland Press Ltd
Received:
January 04 2011
Revision Received:
April 19 2011
Accepted:
May 10 2011
Accepted Manuscript online:
May 10 2011
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2011 Biochemical Society
2011
Biochem J (2011) 437 (3): 493–503.
Article history
Received:
January 04 2011
Revision Received:
April 19 2011
Accepted:
May 10 2011
Accepted Manuscript online:
May 10 2011
Citation
Danielle M. Williams, Heath Ecroyd, Katy L. Goodwin, Huanqin Dai, Haian Fu, Joanna M. Woodcock, Lixin Zhang, John A. Carver; NMR spectroscopy of 14-3-3ζ reveals a flexible C-terminal extension: differentiation of the chaperone and phosphoserine-binding activities of 14-3-3ζ. Biochem J 1 August 2011; 437 (3): 493–503. doi: https://doi.org/10.1042/BJ20102178
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