THE STRUCTURE OF CYCLIN-H - COMMON-MODE OF KINASE ACTIVATION AND SPECIFIC FEATURES

The crystal structure of human cyclin H refined at 2.6 Angstrom resolu tion is compared with that of cyclin A. The core of the molecule consi sts of two repeats containing five helices each and forming the canoni cal cyclin fold also observed in TFIIB. One hundred and thirty-two out of the 217 C alpha atoms from the cyclin fold can be superposed with a root-mean-square difference of 1.8 Angstrom. The structural homology is even higher for the residues at the interface with the kinase, whi ch is of functional significance, as shown by our observation that cyc lin H binds to cyclin-dependent kinase 2 (cdk2) and that cyclin A is a ble to activate cdk7 in the presence of MAT1. Based on this superposit ion, a new signature sequence for cyclins was found, The specificity o f the cyclin H molecule is provided mainly by two long helices which e xtend the cyclin fold at its N- and C-termini and pack together agains t the first repeat on the side opposite to the kinase. Deletion mutant s show that the terminal helices are required for a functionally activ e cyclin H.