The crystal structure of the Physarum polycephalum actin-fragmin kinase:: an atypical protein kinase with a specialized substrate-binding domain

Coordinated temporal and spatial regulation of the actin cytoskeleton is essential for diverse cellular processes such as cell division, cell motility and the formation and maintenance of specialized structures in differentiated cells. In plasmodia of Physarum polycephalum, the F-actin capping activity of the actin-fragmin complex is regulated by the phosphorylation of actin, This is mediated by a novel type of protein kinase with no sequence homology to eukaryotic-type protein kinases, Here we present the crystal structure of the catalytic domain of the first cloned actin kinase in complex with AMP at 2.9 Angstrom resolution. The three-dimensional fold reveals a catalytic module of similar to 160 residues, in common with the eukaryotic protein kinase superfamily, which harbours the nucleotide binding site and the catalytic apparatus in an inter-lobe cleft. Several kinases that share this catalytic module differ in the overall architecture of their substrate recognition domain. The actin-fragmin kinase has acquired a unique Bat substrate recognition domain which is supposed to confer stringent substrate specificity.