1IXV

Crystal Structure Analysis of homolog of oncoprotein gankyrin, an interactor of Rb and CDK4/6


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.234 
  • R-Value Work: 0.194 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Crystal structure of the homolog of the oncoprotein gankyrin, an interactor of Rb and CDK4/6

Padmanabhan, B.Adachi, N.Kataoka, K.Horikoshi, M.

(2004) J Biol Chem 279: 1546-1552

  • DOI: https://doi.org/10.1074/jbc.M310266200
  • Primary Citation of Related Structures:  
    1IXV

  • PubMed Abstract: 

    The oncoprotein gankyrin plays a central role in tumorigenesis and cell proliferation. Gankyrin interacts with the retinoblastoma tumor suppressor (Rb) and cyclin-dependent kinase 4/6 (CDK4/6), increases phosphorylation at specific residues of Rb by CDK4/6 in vivo, and promotes tumorigenesis. The phosphorylation of Rb by CDK4/6 leads to the deregulation of the cell cycle during G1/S transition. Although how phosphorylation occurs on Rb has been studied extensively, the mechanism of site-specific phosphorylation of Rb remains unclear due to a lack of information on the structural arrangement of Rb and CDK4/6. Here, we have determined and refined to 2.3-A resolution the crystal structure of a gankyrin homolog, the non-ATPase subunit 6 (Nas6p) of the proteasome from yeast. The crystal structure reveals that Nas6p contains seven ankyrin repeats. The number of the repeats is different from that predicted from the primary structure. Nas6p also possesses an unusual curved structure with two acidic regions at the N- and C-terminal regions separated by one basic region, suggesting that it has at least two functional surfaces. The tertiary structure of Nas6p, together with the previous biochemical studies, indicates that the CDK4/6 and Rb binding surfaces of gankyrin are located at the N- and C-terminal regions, respectively, and face the same side of gankyrin. These observations suggest that gankyrin brings Rb and CDK4/6 together through gankyrin-Rb and gankyrin-CDK4/6 interactions and determines the relative positioning of the substrate (Rb) and the enzyme (CDK4/6). Our findings provide mechanistic insight into site-specific phosphorylation of Rb caused by CDK4/6.


  • Organizational Affiliation

    Horikoshi Gene Selector Project, Exploratory Research for Advanced Technology, Japan Science and Technology Corp., 5-9-6 Tokodai, Tsukuba, Ibaraki 300-2635, Japan.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Probable 26S proteasome regulatory subunit p28231Saccharomyces cerevisiaeMutation(s): 0 
UniProt
Find proteins for P50086 (Saccharomyces cerevisiae (strain ATCC 204508 / S288c))
Explore P50086 
Go to UniProtKB:  P50086
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP50086
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.234 
  • R-Value Work: 0.194 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 41.433α = 90
b = 61.736β = 90
c = 98.095γ = 90
Software Package:
Software NamePurpose
SCALAdata scaling
SOLVEphasing
CCP4model building
CNSrefinement
CCP4data scaling
CCP4phasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2003-12-16
    Type: Initial release
  • Version 1.1: 2008-04-27
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-12-27
    Changes: Data collection, Database references