1N4M

Structure of Rb tumor suppressor bound to the transactivation domain of E2F-2

Summary for 1N4M

• Entry DOI: 10.2210/pdb1n4m/pdb
• Descriptor: Retinoblastoma Pocket, Transcription factor E2F2 (3 entities in total)
• Functional Keywords: protein-peptide complex, cell cycle
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: Q14209
• Total number of polymer chains: 5
• Total formula weight: 86735.13

Authors

Lee, C.,Chang, J.H.,Lee, H.S.,Cho, Y. (deposition date: 2002-10-31, release date: 2003-01-07, Last modification date: 2024-02-14)

Primary citation

Lee, C.,Chang, J.H.,Lee, H.S.,Cho, Y.
Structural basis for the recognition of the E2F transactivation domain by the retinoblastoma tumor suppressor
GENES DEV., 16:3199-3212, 2002

PubMed Abstract: Repression of E2F transcription activity by the retinoblastoma (Rb) tumor suppressor through its interaction with the transactivation domain of the E2F transcription factor is one of the central features of G1/S arrest in the mammalian cell cycle. Deregulation of the Rb-E2F interaction results in hyperproliferation, lack of differentiation, and apoptosis, and can lead to cancer. The 2.2-A crystal structure of the Rb pocket complexed with an 18-residue transactivation-domain peptide of E2F-2 reveals that the boomerang-shaped peptide binds to the highly conserved interface between the A-box and the B-box of the Rb pocket in a bipartite manner. The N-terminal segment of the E2F-2 peptide in an extended beta-strand-like structure interacts with helices from the conserved groove at the A-B interface, whereas the C-terminal segment, which contains one 3(10) helix, binds to a groove mainly formed by A-box helices. The flexibility in the middle of the E2F-2 peptide is essential for the tight association of E2F to the Rb pocket. The binding of Rb to the E2F-2 peptide conceals several conserved residues that are crucial for transcription activation of E2F. We provide the structural basis for the Rb-mediated repression of E2F transcription activity without the requirement of histone-modifying enzymes.

PubMed: 12502741
DOI: 10.1101/gad.1046102

Experimental method

X-RAY DIFFRACTION (2.2 Å)