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 A resolution. The three-dimensional fold reveals a catalytic module of approximately 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 flat substrate recognition domain which is supposed to confer stringent substrate specificity.
Steinbacher
S
S
Abteilung Strukturforschung, Max-Planck-Institut für Biochemie, 82152 Martinsried, Germany.
Hof
P
P
Eichinger
L
L
Schleicher
M
M
Gettemans
J
J
Vandekerckhove
J
J
Huber
R
R
Benz
J
J
D000249:Adenosine Monophosphate / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D020134:Catalytic Domain; D017124:Conserved Sequence; D003460:Crystallization; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010766:Phosphorylation; D016839:Physarum polycephalum / Q000201:enzymology*; D011487:Protein Conformation; D017510:Protein Folding; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000378:metabolism; D017433:Protein Structure, Secondary
D000249:Adenosine Monophosphate; C074377:actin kinase; D017346:Protein Serine-Threonine Kinases