PDBsum entry: 1bu2

Cell cycle regulation

PDB id: 1bu2

Contents

Protein chain

229 a.a. *

* Residue conservation analysis

PDB id:

1bu2

Name:

Cell cycle regulation

Title:

X-ray structure of a viral cyclin from herpesvirus saimiri

Structure:

Cyclin homolog. Chain: a. Engineered: yes

Source:

Herpesvirus saimiri (strain 11). Organism_taxid: 10383. Strain: 11. Gene: eclf2. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

3.00Å R-factor: 0.242 R-free: 0.325

Authors:

U.Schulze-Gahmen,J.U.Jung,S.-H.Kim

Key ref:

U.Schulze-Gahmen et al. (1999). Crystal structure of a viral cyclin, a positive regulator of cyclin-dependent kinase 6. Structure, 7, 245-254. PubMed id: 10368294 DOI: 10.1016/S0969-2126(99)80035-5

Date:

10-Sep-98 Release date: 15-Jun-99

Protein chain

Q01043  (CGH2_SHV21) -  Cyclin homolog

Seq: 254 a.a.

Struc: 229 a.a.

 Gene Ontology (GO) functional annotation 

• Biological process: cell cycle (3 terms)

DOI no: 10.1016/S0969-2126(99)80035-5

Structure 7:245-254 (1999)

PubMed id: 10368294

Crystal structure of a viral cyclin, a positive regulator of cyclin-dependent kinase 6.

U.Schulze-Gahmen, J.U.Jung, S.H.Kim.

ABSTRACT

BACKGROUND: Cyclin-dependent kinases (CDKs) have a central role in cell-cycle control and are activated by complex formation with positive regulatory proteins called cyclins and by phosphorylation. The overexpression and mutation of cyclins and CDKs has been associated with tumorigenesis and oncogenesis. A virus-encoded cyclin (v-cyclin) from herpesvirus saimiri has been shown to exhibit highest sequence homology to type D cyclins and specifically activates CDK6 of host cells to a very high degree. RESULTS: We have determined the first X-ray structure of a v-cyclin to 3.0 A resolution. The structure of the core domains is very similar to those of cyclin A and cyclin H from human cells. To understand the structural basis for the v-cyclin specificity for CDK6 and the insensitivity of the complex to inhibitors of the p21 and INK4 families, a v-cyclin-CDK2 model was built on the basis of the known structures of human cyclin A in complex with CDK2 and the CDK inhibitor p27(Kip1). CONCLUSIONS: Although many critical interactions between cyclin A and CDK2 would be conserved in a v-cyclin-CDK2 complex, some appear sterically or electrostatically unfavorable due to shifts in the backbone conformation or sidechain differences and may contribute to v-cyclin selectivity for CDK6. The insensitivity of v-cyclin-CDK6 complexes to inhibitors of the p21 family is probably due to structural changes in v-cyclin that lead to a flatter surface area offering fewer potential contacts with the protein inhibitor. In addition, sequence changes in v-cyclin eliminate hydrogen-bonding partners for atoms of the p27(Kip1) inhibitor. This structure provides the first model for interactions between v-cyclins and host cell-cycle proteins; these interactions may be important for virus survival as well as oncogenic transformation of host cells.

Selected figure(s)

Figure 5.
Figure 5. Schematic drawing of the molecular contacts between v-cyclin and CDK2 in a model complex based on the cyclin-A–CDK2 complex. v-Cyclin is shown in blue, CDK2 in orange and cyclin A in green. (a) The conserved hydrogen bonds between Glu136 and Lys107 in v-cyclin and the backbone atoms of residues 42–44 in CDK2. The sidechains of residues 42–44 are omitted for clarity. Conserved hydrogen bonds are indicated as broken lines. The dotted line indicates a contact that is too long for a hydrogen bond in the v-cyclin–CDK2 complex, but could probably be formed after minor structural changes in either molecule. (b) Schematic drawing of the close interactions between residues 111–113 in v-cyclin and residues 46–50 in the PSTAIRE helix of CDK2, the T loop residues 159–162 and Arg150. The backbone structure of cyclin A is shown for comparison. (c) Potential contact residues for the v-cyclin residue Trp145. Too close contacts with His71 in CDK2 are probably caused by a shift in the Trp145 position due to crystal contacts. If Trp145 is overlapped onto the equivalent Phe304 in cyclin A, more favorable interactions with Ile52 and Val69 in CDK2 can be formed. (d) A patch of closely positioned charged residues in a modeled v-cyclin–CDK2 complex. In particular, residues Arg30 in v-cyclin and Arg122 in CDK2 are in too close contact. (The figures were made using the program MOLSCRIPT [50].)

The above figure is reprinted by permission from Cell Press: Structure (1999, 7, 245-254) copyright 1999.

Figure was selected by an automated process.