The structure of cyclin H: common mode of kinase activation and specific features.
The crystal structure of human cyclin H refined at 2.6 A resolution is compared with that of cyclin A. The core of the molecule consists of two repeats containing five helices each and forming the canonical 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 A. The structural homology is even higher for the residues at the interface with the kinase, which is of functional significance, as shown by our observation that cyclin H binds to cyclin-dependent kinase 2 (cdk2) and that cyclin A is able to activate cdk7 in the presence of MAT1. Based on this superposition, a new signature sequence for cyclins was found. The specificity of the cyclin H molecule is provided mainly by two long helices which extend the cyclin fold at its N- and C-termini and pack together against the first repeat on the side opposite to the kinase. Deletion mutants show that the terminal helices are required for a functionally active cyclin H.
Andersen
G
G
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CU de Strasbourg, France.
Busso
D
D
Poterszman
A
A
Hwang
J R
JR
Wurtz
J M
JM
Ripp
R
R
Thierry
J C
JC
Egly
J M
JM
Moras
D
D
D000595:Amino Acid Sequence; D015153:Blotting, Western; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D056748:Cyclin H; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D016213:Cyclins / Q000737:chemistry* / Q000378:metabolism; D004789:Enzyme Activation / Q000502:physiology*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid; D016415:Sequence Alignment; D017384:Sequence Deletion / Q000235:genetics; D017386:Sequence Homology, Amino Acid
C534751:CCNH protein, human; D056748:Cyclin H; D016213:Cyclins; D011994:Recombinant Proteins; D018844:Cyclin-Dependent Kinases