Structural basis for the inactivation of retinoblastoma tumor suppressor by SV40 large T antigen.
Inactivation of the retinoblastoma (Rb) tumor suppressor by Simian virus 40 (SV40) large T antigen is one of the central features of tumorigenesis induced by SV40. Both the N-terminal J domain and the LxCxE motif of large T antigen are required for inactivation of Rb. The crystal structure of the N-terminal region (residues 7-117) of SV40 large T antigen bound to the pocket domain of Rb reveals that large T antigen contains a four-helix bundle, and residues from helices alpha2 and alpha4 and from a loop containing the LxCxE motif participate in the interactions with Rb. The two central helices and a connecting loop in large T antigen have structural similarities with the J domains of the molecular chaperones DnaJ and HDJ-1, suggesting that large T antigen may use a chaperone mechanism for its biological function. However, there are significant differences between large T antigen and the molecular chaperones in other regions and these differences are likely to provide the specificity needed for large T antigen to inactivate Rb.
Division of Molecular and Life Science, Pohang University of Science and Technology, Hyo-ja dong, San31, Pohang, Seoul, South Korea.
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Kim
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Ahn
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Cho
D000595:Amino Acid Sequence; D000952:Antigens, Polyomavirus Transforming / Q000737:chemistry* / Q000378:metabolism*; D018360:Crystallography, X-Ray; D016161:Genes, Retinoblastoma; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D017433:Protein Structure, Secondary; D016160:Retinoblastoma Protein / Q000737:chemistry* / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013539:Simian virus 40 / Q000502:physiology*
D000952:Antigens, Polyomavirus Transforming; D010446:Peptide Fragments; D016160:Retinoblastoma Protein