The Structure of Cyclin H: Common Mode of Kinase Activation and Specific Features

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 1997 Mar 3

PMID 9118957

Citations 25

Authors

G Andersen

D Busso

A Poterszman

J R Hwang

J M Wurtz

R Ripp

J C Thierry

J M Egly

D Moras

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Fusion Gene Detection in Prostate Cancer Samples Enhances the Prediction of Prostate Cancer Clinical Outcomes from Radical Prostatectomy through Machine Learning in a Multi-Institutional Analysis.

Yu Y, Liu S, Ren B, Nelson J, Jarrard D, Brooks J Am J Pathol. 2023; 193(4):392-403.

PMID: 36681188 PMC: 10123524. DOI: 10.1016/j.ajpath.2022.12.013.

MCTS1 promotes the development of lung adenocarcinoma by regulating E2F1 expression.

Gao C, Dong R, Li Y, Liang J, Tian H Oncol Lett. 2021; 22(1):531.

PMID: 34079590 PMC: 8156638. DOI: 10.3892/ol.2021.12792.

Structure of TFIIK for phosphorylation of CTD of RNA polymerase II.

van Eeuwen T, Li T, Kim H, Gorbea Colon J, Parker M, Dunbrack R Sci Adv. 2021; 7(15).

PMID: 33827808 PMC: 8026125. DOI: 10.1126/sciadv.abd4420.

Structural basis for CDK7 activation by MAT1 and Cyclin H.

Peissert S, Schlosser A, Kendel R, Kuper J, Kisker C Proc Natl Acad Sci U S A. 2020; 117(43):26739-26748.

PMID: 33055219 PMC: 7604442. DOI: 10.1073/pnas.2010885117.

The cryoelectron microscopy structure of the human CDK-activating kinase.

Greber B, Perez-Bertoldi J, Lim K, Iavarone A, Toso D, Nogales E Proc Natl Acad Sci U S A. 2020; 117(37):22849-22857.

PMID: 32855301 PMC: 7502720. DOI: 10.1073/pnas.2009627117.

References

Feaver W, Svejstrup J, Henry N, Kornberg R . Relationship of CDK-activating kinase and RNA polymerase II CTD kinase TFIIH/TFIIK. Cell. 1994; 79(6):1103-9. DOI: 10.1016/0092-8674(94)90040-x. View

Meijer L . Chemical inhibitors of cyclin-dependent kinases. Trends Cell Biol. 1996; 6(10):393-7. DOI: 10.1016/0962-8924(96)10034-9. View

Svejstrup J, Vichi P, Egly J . The multiple roles of transcription/repair factor TFIIH. Trends Biochem Sci. 1996; 21(9):346-50. View

Nikolov D, Chen H, Halay E, Usheva A, Hisatake K, Lee D . Crystal structure of a TFIIB-TBP-TATA-element ternary complex. Nature. 1995; 377(6545):119-28. DOI: 10.1038/377119a0. View

Andersen G, Poterszman A, Egly J, Moras D, Thierry J . The crystal structure of human cyclin H. FEBS Lett. 1996; 397(1):65-9. DOI: 10.1016/s0014-5793(96)01143-x. View

Nigg E . Cyclin-dependent protein kinases: key regulators of the eukaryotic cell cycle. Bioessays. 1995; 17(6):471-80. DOI: 10.1002/bies.950170603. View

Schaeffer L, Roy R, Humbert S, Moncollin V, Vermeulen W, Hoeijmakers J . DNA repair helicase: a component of BTF2 (TFIIH) basic transcription factor. Science. 1993; 260(5104):58-63. DOI: 10.1126/science.8465201. View

Flores T, Orengo C, Moss D, Thornton J . Comparison of conformational characteristics in structurally similar protein pairs. Protein Sci. 1993; 2(11):1811-26. PMC: 2142289. DOI: 10.1002/pro.5560021104. View

Kabsch W, Sander C . Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers. 1983; 22(12):2577-637. DOI: 10.1002/bip.360221211. View

10.

Jones T, Zou J, Cowan S, Kjeldgaard M . Improved methods for building protein models in electron density maps and the location of errors in these models. Acta Crystallogr A. 1991; 47 ( Pt 2):110-9. DOI: 10.1107/s0108767390010224. View

11.

Jeffrey P, Russo A, Polyak K, Gibbs E, Hurwitz J, Massague J . Mechanism of CDK activation revealed by the structure of a cyclinA-CDK2 complex. Nature. 1995; 376(6538):313-20. DOI: 10.1038/376313a0. View

12.

Nigg E . Cyclin-dependent kinase 7: at the cross-roads of transcription, DNA repair and cell cycle control?. Curr Opin Cell Biol. 1996; 8(3):312-7. DOI: 10.1016/s0955-0674(96)80003-2. View

13.

Evans S . SETOR: hardware-lighted three-dimensional solid model representations of macromolecules. J Mol Graph. 1993; 11(2):134-8, 127-8. DOI: 10.1016/0263-7855(93)87009-t. View

14.

Devereux J, Haeberli P, SMITHIES O . A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984; 12(1 Pt 1):387-95. PMC: 321012. DOI: 10.1093/nar/12.1part1.387. View

15.

Fisher R, MORGAN D . A novel cyclin associates with MO15/CDK7 to form the CDK-activating kinase. Cell. 1994; 78(4):713-24. DOI: 10.1016/0092-8674(94)90535-5. View

16.

Fisher R, Jin P, Chamberlin H, MORGAN D . Alternative mechanisms of CAK assembly require an assembly factor or an activating kinase. Cell. 1995; 83(1):47-57. DOI: 10.1016/0092-8674(95)90233-3. View

17.

Bairoch A, Bucher P, Hofmann K . The PROSITE database, its status in 1995. Nucleic Acids Res. 1996; 24(1):189-96. PMC: 145570. DOI: 10.1093/nar/24.1.189. View

18.

Drapkin R, Reardon J, Ansari A, Huang J, Zawel L, Ahn K . Dual role of TFIIH in DNA excision repair and in transcription by RNA polymerase II. Nature. 1994; 368(6473):769-72. DOI: 10.1038/368769a0. View

19.

Miller S, Lesk A, Janin J, Chothia C . The accessible surface area and stability of oligomeric proteins. Nature. 1987; 328(6133):834-6. DOI: 10.1038/328834a0. View

20.

Altschul S, Boguski M, Gish W, Wootton J . Issues in searching molecular sequence databases. Nat Genet. 1994; 6(2):119-29. DOI: 10.1038/ng0294-119. View