Crystal structure of mouse dual-specificity tyrosine phosphorylation-regulated kinase 1A (mDYRK1A)

DYRK1A, a proline-directed serine/threonine and tyrosine kinase located within the Down syndrome critical region (DSCR) on chromosome 21, plays critical roles in neuronal development and brain physiology. While structural studies on human DYRK1A have been extensively conducted, structural data for its mouse homolog remain unreported. In this study, we present the first crystal structure of mouse DYRK1A (mDYRK1A) encompassing residues 117-481 at a resolution of 3.0 Å. The crystallographic analysis revealed high conservation between mDYRK1A and human DYRK1A (hDYRK1A), with a 99% sequence identity, but identified a distinct structural variation attributable to a single amino acid substitution (S404 in mDYRK1A versus N404 in hDYRK1A). This substitution influences hydrogen bonding and tertiary structure, particularly within the CMGC-specific insertion region. Our findings underscore the importance of this residue in modulating structural stability and crystal packing. This study provides valuable insights into structural dynamics of DYRK1A and lays the groundwork for future studies on functional implications in mouse models of human diseases.