The crystal structure of human cyclin B.
Cyclin B is the key regulatory protein controlling mitosis in all eukaryotes, where it binds cyclin-dependent kinase, cdk1, forming a complex which initiates the mitotic program through phosphorylation of select proteins. Cyclin B regulates the activation, subcellular localization, and substrate specificity of cdk1, and destruction of cyclin B is necessary for mitotic exit. Overexpression of human cyclin B1 has been found in numerous cancers and has been associated with tumor aggressiveness. Here we report the crystal structure of human cyclin B1 to 2.9 A. Comparison of the structure with cyclin A and cyclin E reveals remarkably similar N-terminal cyclin box motifs but significant differences among the C-terminal cyclin box lobes. Divergence in sequence gives rise to unique interaction surfaces at the proposed cyclin B/cdk1 interface as well as the 'RxL' motif substrate binding site on cyclin B. Examination of the structure provides insight into the molecular basis for differential affinities of protein based cyclin/cdk inhibitors such as p27, substrate recognition, and cdk interaction.
Petri
Edward T
ET
Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
Errico
Alessia
A
Escobedo
Lourdes
L
Hunt
Tim
T
Basavappa
Ravi
R
D000595:Amino Acid Sequence; D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism; D016384:Consensus Sequence; D003460:Crystallization; D018360:Crystallography, X-Ray; D019925:Cyclin A / Q000737:chemistry; D019926:Cyclin B / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology; D056744:Cyclin B1; D019927:Cyclin E / Q000737:chemistry; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004926:Escherichia coli; D005260:Female; D006657:Histones / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009865:Oocytes / Q000201:enzymology; D010766:Phosphorylation; D011487:Protein Conformation; D011494:Protein Kinases / Q000032:analysis; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000302:isolation & purification; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012995:Solubility; D013329:Structure-Activity Relationship; D014982:Xenopus laevis
C534699:CCNB1 protein, human; D019925:Cyclin A; D019926:Cyclin B; D056744:Cyclin B1; D019927:Cyclin E; D006657:Histones; D011993:Recombinant Fusion Proteins; D011494:Protein Kinases; C102333:histone H1 kinase; D016203:CDC2 Protein Kinase; D018844:Cyclin-Dependent Kinases