1 research outputs found
Monomeric 14-3-3ζ Has a Chaperone-Like Activity and Is Stabilized by Phosphorylated HspB6
Members of the 14-3-3 eukaryotic protein family predominantly
function
as dimers. The dimeric form can be converted into monomers upon phosphorylation
of Ser<sup>58</sup> located at the subunit interface. Monomers are
less stable than dimers and have been considered to be either less
active or even inactive during binding and regulation of phosphorylated
client proteins. However, like dimers, monomers contain the phosphoserine-binding
site and therefore can retain some functions of the dimeric 14-3-3.
Furthermore, 14-3-3 monomers may possess additional functional roles
owing to their exposed intersubunit surfaces. Previously we have found
that the monomeric mutant of 14-3-3ζ (14-3-3ζ<sub>m</sub>), like the wild type protein, is able to bind phosphorylated small
heat shock protein HspB6 (pHspB6), which is involved in the regulation
of smooth muscle contraction and cardioprotection. Here we report
characterization of the 14-3-3ζ<sub>m</sub>/pHspB6 complex by
biophysical and biochemical techniques. We find that formation of
the complex retards proteolytic degradation and increases thermal
stability of the monomeric 14-3-3, indicating that interaction with
phosphorylated targets could be a general mechanism of 14-3-3 monomers
stabilization. Furthermore, by using myosin subfragment 1 (S1) as
a model substrate we find that the monomer has significantly higher
chaperone-like activity than either the dimeric 14-3-3ζ protein
or even HspB6 itself. These observations indicate that 14-3-3ζ
and possibly other 14-3-3 isoforms may have additional functional
roles conducted by the monomeric state