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 es sential for diverse cellular processes such as cell division, cell motility and the formation and maintenance of specialized structures in differentia ted cells. In plasmodia of Physarum polycephalum, the F-actin capping activ ity of the actin-fragmin complex is regulated by the phosphorylation of act in, This is mediated by a novel type of protein kinase with no sequence hom ology to eukaryotic-type protein kinases, Here we present the crystal struc ture of the catalytic domain of the first cloned actin kinase in complex wi th AMP at 2.9 Angstrom resolution. The three-dimensional fold reveals a cat alytic module of similar to 160 residues, in common with the eukaryotic pro tein kinase superfamily, which harbours the nucleotide binding site and the catalytic apparatus in an inter-lobe cleft. Several kinases that share thi s catalytic module differ in the overall architecture of their substrate re cognition domain. The actin-fragmin kinase has acquired a unique Bat substr ate recognition domain which is supposed to confer stringent substrate spec ificity.