Patient-Derived Variants Define Constraints for Ligand Binding at the PDZ Domain of CASK.

ABSTRACT: Genetic variants in the X-chromosomal gene coding for the calcium-/calmodulin-dependent serine protein kinase (CASK) are associated with a neurodevelopmental disorder. CASK is a member of the membrane-associated guanylate kinase (MAGUK) family of proteins. It acts as a scaffold at presynaptic sites, as a regulator of the transport of glutamate receptors, and as a transcriptional regulator. The PDZ domain of CASK has been reported to bind to presynaptic cell adhesion molecules such as Neurexin1-3, CNTNAP2, SynCAM and SALM1. Structural analyses of related MAGUKs indicate that the canonical SH3 and GK domains combine with the PDZ domain to form the so-called PSG supramodule. Conserved aromatic residues (Y723 and W914) flanking the GK domain contribute to the formation of a dimeric structure o

SUBMITTER: Tibbe D 

PROVIDER: S-EPMC12666738 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature