CYCLIN-DEPENDENT KINASE-5 (CDKB) ACTIVATION DOMAIN OF NEURONAL CDK5 ACTIVATOR - EVIDENCE OF THE EXISTENCE OF CYCLIN FOLD IN NEURONAL CDK5A ACTIVATOR

Neuronal Cdk5 activator (Nck5a) differs from other cyclin-dependent ki nase (Cdk) activators in that its amino acid sequence is only marginal ly similar to the cyclin consensus sequence, Nevertheless, computer mo deling has suggested that Nck5a contains the cyclin-fold motif recentl y identified in the crystal structure of cyclin A. In the present stud y, a number of truncation mutants and substitution mutants of the Nck5 a were produced and tested for the Cdk5 activation and Cdk5 binding ac tivity, The active domain of Nck5a determined by using the truncation mutants consists of the region spanning residues 150 to 291. The size of Nck5a active domain is essentially the same as that of cyclin A req uired for Cdk2 activation (Lees, E. M., and Harlow, E. (1993) Mol. Cel l. Biol. 13, 1194-1201). The change, or the lack of change, in Cdk5 ac tivation activity observed with a number of substitution mutants may b e understood on the basis of structure and function relationship of cy clin A, These results provide support to the previous suggestion (Brow n, N. R., Noble, M. E. M., Endicott, J. A., Garman, E. F., Wakatsuki, S., Mitchell, E., Rasmussen, B., Hunt, T., and Johnson, L. N. (1995) S tructure 3, 1235-1247) that the activation domain of Nck5a adopts a co nformation similar to that of cyclin A, They also provide a partial an swer to the question of how Nck5a, a non-cyclin, activates a cyclin-de pendent kinase.