Neutral trehalase 1 (Nth1) from Saccharomyces cerevisiae
catalyzes disaccharide trehalose hydrolysis and helps yeast to
survive adverse conditions, such as heat shock, starvation or
oxidative stress. 14-3-3 proteins, master regulators of hundreds
of partner proteins, participate in many key cellular processes.
Nth1 is activated by phosphorylation followed by 14-3-3 protein
(Bmh) binding. The activation mechanism is also potentiated by
Ca2+ binding within the EF-hand-like motif. This review
summarizes the current knowledge about trehalases and the
molecular and structural basis of Nth1 activation. The crystal
structure of fully active Nth1 bound to 14-3-3 protein provided
the first high-resolution view of a trehalase from a eukaryotic
organism and showed 14-3-3 proteins as structural modulators
and allosteric effectors of multi-domain binding partners.