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The structure of cyclin H: common mode of kinase activation and specific features
Author(s) -
Andersen Gregers,
Busso Didier,
Poterszman Arnaud,
Hwang Jae Ryoung,
Wurtz JeanMarie,
Ripp Raymond,
Thierry JeanClaude,
Egly JeanMarc,
Moras Dino
Publication year - 1997
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/16.5.958
Subject(s) - cyclin a , cyclin dependent kinase complex , biology , cyclin dependent kinase , cyclin a2 , cyclin d , cyclin b , cyclin , cyclin e , microbiology and biotechnology , biochemistry , cyclin dependent kinase 2 , kinase , cell cycle , protein kinase a , cell
The crystal structure of human cyclin H refined at 2.6 Å 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 Cα atoms from the cyclin fold can be superposed with a root‐mean‐square difference of 1.8 Å. 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.