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1ixv

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[[Image:1ixv.gif|left|200px]]
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{{STRUCTURE_1ixv| PDB=1ixv | SCENE= }}
{{STRUCTURE_1ixv| PDB=1ixv | SCENE= }}
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'''Crystal Structure Analysis of homolog of oncoprotein gankyrin, an interactor of Rb and CDK4/6'''
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===Crystal Structure Analysis of homolog of oncoprotein gankyrin, an interactor of Rb and CDK4/6===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 14583612 is the PubMed ID number.
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{{ABSTRACT_PUBMED_14583612}}
==About this Structure==
==About this Structure==
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[[Category: Padmanabhan, B.]]
[[Category: Padmanabhan, B.]]
[[Category: Ankyrin repeat]]
[[Category: Ankyrin repeat]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 20:33:28 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 14:11:35 2008''

Revision as of 11:11, 1 July 2008

Image:1ixv.png

Template:STRUCTURE 1ixv

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

Template:ABSTRACT PUBMED 14583612

About this Structure

1IXV is a Single protein structure of sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA.

Reference

Crystal structure of the homolog of the oncoprotein gankyrin, an interactor of Rb and CDK4/6., Padmanabhan B, Adachi N, Kataoka K, Horikoshi M, J Biol Chem. 2004 Jan 9;279(2):1546-52. Epub 2003 Oct 28. PMID:14583612

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