Andersen G, Busso D, Poterszman A, Hwang J R, Wurtz J M, Ripp R, Thierry J C, Egly J M, Moras D
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CU de Strasbourg, France.
EMBO J. 1997 Mar 3;16(5):958-67. doi: 10.1093/emboj/16.5.958.
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.
将分辨率为2.6埃的人细胞周期蛋白H的晶体结构与细胞周期蛋白A的晶体结构进行了比较。该分子的核心由两个重复序列组成，每个重复序列包含五个螺旋，并形成了在TFIIB中也观察到的典型细胞周期蛋白折叠结构。细胞周期蛋白折叠结构中的217个Cα原子中有132个可以重叠，均方根偏差为1.8埃。与激酶相互作用界面处的残基结构同源性更高，这具有功能意义，正如我们观察到细胞周期蛋白H与细胞周期蛋白依赖性激酶2（cdk2）结合，以及细胞周期蛋白A在MAT1存在的情况下能够激活cdk7所表明的那样。基于这种重叠，发现了一种新的细胞周期蛋白特征序列。细胞周期蛋白H分子的特异性主要由两个长螺旋提供，这两个长螺旋在其N端和C端延伸细胞周期蛋白折叠结构，并在与激酶相对的一侧与第一个重复序列靠在一起。缺失突变体表明，末端螺旋是具有功能活性的细胞周期蛋白H所必需的。
