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Structural basis for the inactivation of retinoblastoma tumor suppressor by SV40 large T antigen
Author(s) -
Kim HyeYeon,
Ahn ByungYoon,
Cho Yunje
Publication year - 2001
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/20.1.295
Subject(s) - biology , sv40 large t antigen , antigen , retinoblastoma , retinoblastoma protein , suppressor , microbiology and biotechnology , carcinogenesis , genetics , gene , cell cycle , transfection
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 α2 and α4 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.