A Conserved Allosteric Pathway in Tyrosine Kinase Regulation (Structure)

Marsiglia et al. reveal that the kinase molecular brake is coupled to the DFG motif through an allosteric pathway involving an isoleucine residue that locks the phenylalanine of the DFG motif activation loop in an inactive conformation. Pathogenic mutations that target the molecular brake activate the enzyme by perturbing this allosteric network.