Dynamic structural properties of 14-3-3 zeta protein underpin its molecular chaperone action against amorphous protein aggregation
- Centre for Cancer Biology, SA Pathology and University of South Australia, SA.
- School of Physical Sciences, University of Adelaide, SA.
- Walter and Eliza Hall Institute of Medical Research, Parkville, VIC.
- Australian Nuclear and Science Technology Organisation, NSW.
- Research School of Chemistry, Australian National University, Canberra, ACT.
The family of 14-3-3 proteins are dimeric phospho-serine binding proteins that function as adaptors with important roles in the regulation of many signaling responses in eukaryotic cells. Less well described, 14-3-3 proteins also exhibit molecular chaperone activity that attenuates the amorphous aggregation of proteins. This property may explain the occurrence of the 14-3-3 zeta isoform in the pathological protein aggregation associated with neurodegenerative conditions including Alzheimer’s and Parkinson’s diseases. To better understand this aspect of 14-3-3 proteins’ function, we have examined the regions of 14-3-3 zeta that play a role in its molecular chaperone action. We determined that neither the flexible C-terminus region nor the amphipathic phospho-serine binding groove contribute to molecular chaperone action. Published studies using mutant forms of 14-3-3 zeta that are engineered to disrupt the dimeric state of the protein suggest that monomeric 14-3-3 zeta represents the chaperone-competent form of the protein. However, our recent results suggest that this is a simplistic view and that the dimer interface of 14-3-3 zeta represents a structurally dynamic region that is involved simultaneously in both 14-3-3 protein dimer formation and molecular chaperone function.