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PMID: 11226179 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Structural basis for the inactivation of retinoblastoma tumor suppressor by SV40 large T antigen.

The EMBO journal ·Vol. 20 ·No. 1-2 ·2001-01-15 ·Pages 295-304

Kim HY, Ahn BY, Cho Y

Abstract

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.

MeSH Terms
Amino Acid Sequence Antigens, Polyomavirus Transforming/chemistry,metabolism Crystallography, X-Ray Genes, Retinoblastoma Humans Models, Molecular Molecular Sequence Data Peptide Fragments/chemistry,metabolism Protein Structure, Secondary Retinoblastoma Protein/chemistry,metabolism Sequence Alignment Sequence Homology, Amino Acid Simian virus 40/physiology
Chemicals
Antigens, Polyomavirus Transforming Peptide Fragments Retinoblastoma Protein
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Kim H Y
Division of Molecular and Life Science, Pohang University of Science and Technology, Hyo-ja dong, San31, Pohang, Seoul, South Korea.
Ahn B Y
Cho Y
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/20.1.295
Published
2001-01-15
Pages
295-304
Language
English
Region
England
NLM ID
8208664
PMCID
PMC140208
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/20.1.295 PMC Full Text View journal details
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