6FQP

Crystal structure of TALE homeobox domain transcription factor TGIF1 with its consensus DNA

Summary for 6FQP

• Entry DOI: 10.2210/pdb6fqp/pdb
• Descriptor: DNA (5'-D(P*AP*TP*TP*GP*AP*CP*AP*GP*CP*TP*GP*TP*CP*AP*AP*T)-3'), Homeobox protein TGIF1, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: homeobox, three-amino acid loop extension, tgf-beta pathway, transcription
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 33293.16

Authors

Guca, E.,Macias, M.J. (deposition date: 2018-02-14, release date: 2018-07-25, Last modification date: 2024-01-17)

Primary citation

Guca, E.,Sunol, D.,Ruiz, L.,Konkol, A.,Cordero, J.,Torner, C.,Aragon, E.,Martin-Malpartida, P.,Riera, A.,Macias, M.J.
TGIF1 homeodomain interacts with Smad MH1 domain and represses TGF-beta signaling.
Nucleic Acids Res., 46:9220-9235, 2018

PubMed Abstract: TGIF1 is a multifunctional protein that represses TGF-β-activated transcription by interacting with Smad2-Smad4 complexes. We found that the complex structure of TGIF1-HD bound to the TGACA motif revealed a combined binding mode that involves the HD core and the major groove, on the one hand, and the amino-terminal (N-term) arm and the minor groove of the DNA, on the other. We also show that TGIF1-HD interacts with the MH1 domain of Smad proteins, thereby indicating that TGIF1-HD is also a protein-binding domain. Moreover, the formation of the HD-MH1 complex partially hinders the DNA-binding site of the complex, preventing the efficient interaction of TGIF1-HD with DNA. We propose that the binding of the TGIF1 C-term to the Smad2-MH2 domain brings both the HD and MH1 domain into close proximity. This local proximity facilitates the interaction of these DNA-binding domains, thus strengthening the formation of the protein complex versus DNA binding. Once the protein complex has been formed, the TGIF1-Smad system would be released from promoters/enhancers, thereby illustrating one of the mechanisms used by TGIF1 to exert its function as an active repressor of Smad-induced TGF-β signaling.

PubMed: 30060237
DOI: 10.1093/nar/gky680

Experimental method

X-RAY DIFFRACTION (2.42 Å)