|کد مقاله||کد نشریه||سال انتشار||مقاله انگلیسی||ترجمه فارسی||نسخه تمام متن|
|5370629||1503897||2017||5 صفحه PDF||سفارش دهید||دانلود کنید|
- Disordered part of regulatory domain of human tyrosine hydroxylase 1 was assigned.
- Transient alpha-helices are present next to phosphorylation sites S40 and S19.
- The secondary structure does not change after phosphorylation.
- The phosphorylation kinetic rates were measured efficiently using time resolved NMR.
Human tyrosine hydroxylase 1 (hTH1) activity is regulated by phosphorylation of its regulatory domain (RD-hTH1) and by an interaction with the 14-3-3 protein. The RD-hTH1 is composed of a structured region (66-169) preceded by an intrinsically disordered protein region (IDP, hTH1_65) containing two phosphorylation sites (S19 and S40) which are highly relevant for its increase in activity. The NMR signals of the IDP region in the non-phosphorylated, singly phosphorylated (pS40) and doubly phosphorylated states (pS19_pS40) were assigned by non-uniformly sampled spectra with increased dimensionality (5D). The structural changes induced by phosphorylation were analyzed by means of secondary structure propensities. The phosphorylation kinetics of the S40 and S19 by kinases PKA and PRAK respectively were monitored by non-uniformly sampled time-resolved NMR spectroscopy followed by their quantitative analysis.
Journal: Biophysical Chemistry - Volume 223, April 2017, Pages 25-29