NMR spectroscopy of 14-3-3? reveals a flexible C-terminal extension. Differentiation of the chaperone and phosphoserine binding activities of 14-3-3?
NMR spectroscopy of 14-3-3? reveals a flexible C-terminal extension. Differentiation of the chaperone and phosphoserine binding activities of 14-3-3?
Biochem J. 2011 May 10;
Authors: Williams DM, Ecroyd H, Goodwin KL, Dai H, Fu H, Woodcock JM, Zhang L, Carver JA
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 stress-induced aggregation of target proteins in a comparable manner to the unrelated small heat-shock proteins (sHsps). 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 stabilises 14-3-3? but has no direct role in chaperone action. K49 is an important functional residue within 14-3-3?'s ligand binding groove with K49E 14-3-3? exhibiting markedly reduced binding to phosphorylated and non-phosphorylated ligands. The R18 peptide binds to 14-3-3?'s binding groove with high affinity and also reduces 14-3-3?'s interactions with ligands. However, neither K49E 14-3-3? nor the presence of the R18 peptide affect 14-3-3?'s chaperone activity, 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 involved, i.e. the protein's chaperone and phosphoserine binding activities are functionally and structurally separated.
PMID: 21554249 [PubMed - as supplied by publisher]
Source:
PubMed