Tyrosine hydroxylase variants influence protein expression, cellular localization, stability, enzymatic activity and the physical interaction between tyrosine hydroxylase and GTP cyclohydrolase 1.

Tyrosine hydroxylase (TH) is the rate-limiting enzyme in dopamine biosynthesis catalyzing the tetrahydrobiopterin (BH)-dependent hydroxylation of tyrosine to L-DOPA. Here, we analyzed 25 TH variants associated with various degrees of dopa-responsive dystonia and evaluate the effect of each variant on protein stability, activity and cellular localization. Furthermore, we investigated the physical interaction between TH and human wildtype (wt) GTP cyclohydrolase 1 (GTPCH) and the effect of variants on this interaction.

The BAF chromatin remodeling complexes: structure, function, and synthetic lethalities.

BAF complexes are multi-subunit chromatin remodelers, which have a fundamental role in genomic regulation. Large-scale sequencing efforts have revealed frequent BAF complex mutations in many human diseases, particularly in cancer and neurological disorders. These findings not only underscore the importance of the BAF chromatin remodelers in cellular physiological processes, but urge a more detailed understanding of their structure and molecular action to enable the development of targeted therapeutic approaches for diseases with BAF complex alterations.