Structure of the retinoblastoma protein bound to adenovirus E1A reveals the molecular basis for viral oncoprotein inactivation of a tumor suppressor

Journal Article · Wed Apr 02 00:00:00 EDT 2008 · Gene Dev.

DOI:https://doi.org/10.1101/gad.1590607· OSTI ID:1007633

Liu, Xin; Marmorstein, Ronen ^[1]

---

1. UPENN

The adenovirus (Ad) E1A (Ad-E1A) oncoprotein mediates cell transformation, in part, by displacing E2F transcription factors from the retinoblastoma protein (pRb) tumor suppressor. In this study we determined the crystal structure of the pRb pocket domain in complex with conserved region 1 (CR1) of Ad5-E1A. The structure and accompanying biochemical studies reveal that E1A-CR1 binds at the interface of the A and B cyclin folds of the pRb pocket domain, and that both E1A-CR1 and the E2F transactivation domain use similar conserved nonpolar residues to engage overlapping sites on pRb, implicating a novel molecular mechanism for pRb inactivation by a viral oncoprotein.

• Research Organization: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
• Sponsoring Organization: USDOE
• OSTI ID: 1007633
• Journal Information: Gene Dev., Vol. 27, Issue 11, 2007; ISSN 0890-9369
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

36 MATERIALS SCIENCE
ADENOVIRUS
CELL TRANSFORMATIONS
CRYSTAL STRUCTURE
INACTIVATION
NEOPLASMS
PROTEINS
RESIDUES
TRANSCRIPTION FACTORS