Structure and function of the guanylate kinase-like domain of the MAGUK family scaffold proteins

Membrane associated guanylate kinases (MAGUKs) are a family of scaffold proteins that play essential roles in organ development, cell-cell communication, cell polarity establishment and maintenance, and cellular signal transduction. Every member of the MAGUK family contains a guanylate kinase-like (GK) domain, which has evolved from the enzyme catalyzing GMP to GDP conversion to become a protein-protein interaction module with no enzymatic activity.Mutations of MAGUKs are linked to a number of human diseases, including autism and hereditary deafness. In this review, we summarize the structural basis governing cellular function of various members of the MAGUKs. In particular, we focus on recent discoveries of MAGUK GKs as specific phospho-protein interaction modules, and discuss functional implications and connections to human diseases of such regulated MAGUK GK/target interactions.