Summary information and primary citation
- PDB-id
- 5mez; SNAP-derived features in text and JSON formats;
DNAproDB
- Class
- transcription
- Method
- X-ray (2.98 Å)
- Summary
- Crystal structure of smad4-mh1 bound to the ggct site.
- Reference
- Martin-Malpartida P, Batet M, Kaczmarska Z, Freier R, Gomes T, Aragon E, Zou Y, Wang Q, Xi Q, Ruiz L, Vea A, Marquez JA, Massague J, Macias MJ (2017): "Structural basis for genome wide recognition of 5-bp GC motifs by SMAD transcription factors." Nat Commun, 8, 2070. doi: 10.1038/s41467-017-02054-6.
- Abstract
- Smad transcription factors activated by TGF-β or by BMP receptors form trimeric complexes with Smad4 to target specific genes for cell fate regulation. The CAGAC motif has been considered as the main binding element for Smad2/3/4, whereas Smad1/5/8 have been thought to preferentially bind GC-rich elements. However, chromatin immunoprecipitation analysis in embryonic stem cells showed extensive binding of Smad2/3/4 to GC-rich cis-regulatory elements. Here, we present the structural basis for specific binding of Smad3 and Smad4 to GC-rich motifs in the goosecoid promoter, a nodal-regulated differentiation gene. The structures revealed a 5-bp consensus sequence GGC(GC)|(CG) as the binding site for both TGF-β and BMP-activated Smads and for Smad4. These 5GC motifs are highly represented as clusters in Smad-bound regions genome-wide. Our results provide a basis for understanding the functional adaptability of Smads in different cellular contexts, and their dependence on lineage-determining transcription factors to target specific genes in TGF-β and BMP pathways.
