Dissection of binding between a phosphorylated tyrosine hydroxylase peptide and 14-3-3zeta: A complex story elucidated by NMR.

ABSTRACT: Human tyrosine hydroxylase activity is regulated by phosphorylation of its N-terminus and by an interaction with the modulator 14-3-3 proteins. We investigated the binding of singly or doubly phosphorylated and thiophosphorylated peptides, comprising the first 50 amino acids of human tyrosine hydroxylase, isoform 1 (hTH1), that contain the critical interaction domain, to 14-3-3?, by (31)P NMR. Single phosphorylation at S19 generates a high affinity 14-3-3? binding epitope, whereas singly S40-phosphorylated peptide interacts with 14-3-3? one order-of-magnitude weaker than the S19-phosphorylated peptide. Analysis of the binding data revealed that the 14-3-3? dimer and the S19- and S40-doubly phosphorylated peptide interact in multiple ways, with three major complexes formed: 1), a single pep

SUBMITTER: Hritz J 

PROVIDER: S-EPMC4223184 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature