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PDBsum entry 1n4m
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Structural basis for the recognition of the e2f transactivation domain by the retinoblastoma tumor suppressor.
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Authors
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C.Lee,
J.H.Chang,
H.S.Lee,
Y.Cho.
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Ref.
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Genes Dev, 2002,
16,
3199-3212.
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PubMed id
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Abstract
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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.
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