7CO1

Crystal structure of SMAD2 in complex with wild-type CBP

Summary for 7CO1

• Entry DOI: 10.2210/pdb7co1/pdb
• Descriptor: Mothers against decapentaplegic homolog 2, CREB-binding protein (2 entities in total)
• Functional Keywords: tgf-beta, complex, transcription factor, signaling protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 79856.71

Authors

Miyazono, K.,Wada, H.,Ito, T.,Tanokura, M. (deposition date: 2020-08-03, release date: 2020-11-25, Last modification date: 2023-11-29)

Primary citation

Miyazono, K.I.,Ito, T.,Fukatsu, Y.,Wada, H.,Kurisaki, A.,Tanokura, M.
Structural basis for transcriptional coactivator recognition by SMAD2 in TGF-beta signaling.
Sci.Signal., 13:-, 2020

PubMed Abstract: Transforming growth factor-β (TGF-β) proteins regulate multiple cellular functions, including cell proliferation, apoptosis, and extracellular matrix formation. The dysregulation of TGF-β signaling causes diseases such as cancer and fibrosis, and therefore, understanding the biochemical basis of TGF-β signal transduction is important for elucidating pathogenic mechanisms in these diseases. SMAD proteins are transcription factors that mediate TGF-β signaling-dependent gene expression. The transcriptional coactivator CBP directly interacts with the MH2 domains of SMAD2 to activate SMAD complex-dependent gene expression. Here, we report the structural basis for CBP recognition by SMAD2. The crystal structures of the SMAD2 MH2 domain in complex with the SMAD2-binding region of CBP showed that CBP forms an amphiphilic helix on the hydrophobic surface of SMAD2. The expression of a mutated CBP peptide that showed increased SMAD2 binding repressed SMAD2-dependent gene expression in response to TGF-β signaling in cultured cells. Disrupting the interaction between SMAD2 and CBP may therefore be a promising strategy for suppressing SMAD-dependent gene expression.

PubMed: 33323411
DOI: 10.1126/scisignal.abb9043

Experimental method

X-RAY DIFFRACTION (3.3 Å)