Crystal structure of a γ-herpesvirus cyclin-cdk complex

被引：40

作者：

Card, GL

Knowles, P

Laman, H

Jones, N

McDonald, NQ

机构：

[1] Univ London Birkbeck Coll, Dept Crystallog, London WC1E 7HX, England

[2] Imperial Canc Res Fund, Gene Express Labs, London WC2A 3PX, England

来源：

EMBO JOURNAL | 2000年 / 19卷 / 12期

关键词：

cyclin; cyclin-dependent kinase; herpesvirus; p27(Kip); structure;

D O I：

10.1093/emboj/19.12.2877

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Several gamma-herpesviruses encode proteins related to the mammalian cyclins, regulatory subunits of cyclin-dependent kinases (cdks) essential for cell cycle progression. We report a 2.5 Angstrom crystal structure of a full-length oncogenic viral cyclin from gamma-herpesvirus 68 complexed with cdk2. The viral cyclin binds cdk2 with an orientation different from cyclin A and makes several novel interactions at the interface, yet it activates cdk2 by triggering conformational changes similar to cyclin A. Sequences within the viral cyclin N-terminus lock part of the cdk2 T-loop within the core of the complex. These sequences and others are conserved amongst the viral and cellular D-type cyclins, suggesting that this structure has wider implications for other cyclin-cdk complexes. The observed resistance of this viral cyclin-cdk complex to inhibition by the p27(Kip) cdk inhibitor is explained by sequence and conformational variation in the cyclin rendering the p27(Kip)-binding site on the cyclin subunit non-functional.

引用

页码：2877 / 2888

页数：12

共 40 条

[1] HERPESVIRUS SAIMIRI HAS A GENE SPECIFYING A HOMOLOG OF THE CELLULAR MEMBRANE GLYCOPROTEIN CD59 [J].

ALBRECHT, JC ;

NICHOLAS, J ;

CAMERON, KR ;

NEWMAN, C ;

FLECKENSTEIN, B ;

HONESS, RW .

VIROLOGY, 1992, 190 (01) :527-530

[2] The structure of cyclin H: Common mode of kinase activation and specific features [J].

Andersen, G ;

Busso, D ;

Poterszman, A ;

Hwang, JR ;

Wurtz, JM ;

Ripp, R ;

Thierry, JC ;

Egly, JM ;

Moras, D .

EMBO JOURNAL, 1997, 16 (05) :958-967

[3] THE CCP4 SUITE - PROGRAMS FOR PROTEIN CRYSTALLOGRAPHY [J].

BAILEY, S .

ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1994, 50 :760-763

[4] The structural basis for specificity of substrate and recruitment peptides for cyclin-dependent kinases [J].

Brown, NR ;

Noble, MEM ;

Endicott, JA ;

Johnson, LN .

NATURE CELL BIOLOGY, 1999, 1 (07) :438-443

[5] THE CRYSTAL-STRUCTURE OF CYCLIN-A [J].

BROWN, NR ;

NOBLE, MEM ;

ENDICOTT, JA ;

GARMAN, EF ;

WAKATSUKI, S ;

MITCHELL, E ;

RASMUSSEN, B ;

HUNT, T ;

JOHNSON, LN .

STRUCTURE, 1995, 3 (11) :1235-1247

[6] Crystallography & NMR system:: A new software suite for macromolecular structure determination [J].

Brunger, AT ;

Adams, PD ;

Clore, GM ;

DeLano, WL ;

Gros, P ;

Grosse-Kunstleve, RW ;

Jiang, JS ;

Kuszewski, J ;

Nilges, M ;

Pannu, NS ;

Read, RJ ;

Rice, LM ;

Simonson, T ;

Warren, GL .

ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1998, 54 :905-921

[7]

BRUNGER AT, 1996, XPLOR REFERENCE MANU

[8] Cyclin encoded by KS herpesvirus [J].

Chang, Y ;

Moore, PS ;

Talbot, SJ ;

Boshoff, CH ;

Zarkowska, T ;

GoddenKent, D ;

Paterson, H ;

Weiss, RA ;

Mittnacht, S .

NATURE, 1996, 382 (6590) :410-410

[9]

Cowtan K., 1994, JOINT CCP4 ESF EACBM, V31, P34

[10] Degradation of p27Kip cdk inhibitor triggered by Kaposi's sarcoma virus cyclin-cdk6 complex [J].

Ellis, M ;

Chew, YP ;

Fallis, L ;

Freddersdorf, S ;

Boshoff, C ;

Weiss, RA ;

Lu, X ;

Mittnacht, S .

EMBO JOURNAL, 1999, 18 (03) :644-653

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