5NM9

Crystal structure of the placozoa Trichoplax adhaerens Smad4-MH1 bound to the GGCGC site.

Summary for 5NM9

• Entry DOI: 10.2210/pdb5nm9/pdb
• Related: 5MEY 5MEZ 5MF0
• Descriptor: Mothers against decapentaplegic homolog, DNA (5'-D(P*AP*TP*GP*CP*GP*GP*GP*CP*GP*CP*GP*CP*CP*CP*GP*CP*AP*T)-3'), ZINC ION, ... (4 entities in total)
• Functional Keywords: smads, transcription factor, dna complex, transcription
• Biological source: Trichoplax adhaerens; More
• Cellular location: Cytoplasm . Nucleus : B3S7S5
• Total number of polymer chains: 4
• Total formula weight: 43138.81

Authors

Kaczmarska, Z.,Freier, R.,Marquez, J.A.,Macias, M.J. (deposition date: 2017-04-05, release date: 2017-11-15, Last modification date: 2024-01-17)

Primary citation

Martin-Malpartida, P.,Batet, M.,Kaczmarska, Z.,Freier, R.,Gomes, T.,Aragon, E.,Zou, Y.,Wang, Q.,Xi, Q.,Ruiz, L.,Vea, A.,Marquez, J.A.,Massague, J.,Macias, M.J.
Structural basis for genome wide recognition of 5-bp GC motifs by SMAD transcription factors.
Nat Commun, 8:2070-2070, 2017

PubMed 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.

PubMed: 29234012
DOI: 10.1038/s41467-017-02054-6

Experimental method

X-RAY DIFFRACTION (2.43 Å)