Summary information and primary citation

PDB-id
5mf0; SNAP-derived features in text and JSON formats; DNAproDB
Class
transcription
Method
X-ray (3.03 Å)
Summary
Crystal structure of smad4-mh1 bound to the ggccg 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.

Cartoon-block schematics in six views (download the tarball)

PyMOL session file Download PDB file View in 3Dmol.js