 MH1 Domain | |
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Structure:
 The structure shown is the Smad3 MH1 domain in complex with the Smad-binding element (SBE) DNA sequence. Each of the MH1 domains consists of four alpha-helices, six short beta-strands, five loops, and binds identically and independently to the SBE sequence 5’-GTCT-3’ or 5’-AGAC-3’ through hydrogen bonds to the DNA bases and phosphodiester backbone. An 11-residue beta-hairpin, formed between strands B2 and B3, protrudes outward from the globular MH1 core and is responsible for DNA contact. This contact is stabilized by a number of surrounding water molecules. Additionally, a zinc atom is buried deep within the MH1 structure, where in its absence the affinity of the MH1/DNA complex is compromised. Structure Reference: Chai, J. et al. (2003) J. Biol. Chem. 278(22), 20327-20331. PDB: 1OZJ
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Domain binding and function:
The MH1, short for Mad homology 1, domain is typically found at the N-terminus of Smad proteins and is responsible for DNA binding activity as well as negative regulation of the Smad C-terminal MH2 domain. The binding of the MH1 domain is specific to the minimal unique 4-bp sequence called the Smad-box of the sequence 5’-GTCT-3’ or 5’-AGAC-3’. The ability for MH1 to bind the SBE is critical for Smad-mediated activation of specific ligand-responsive genes in TGF-beta signaling. | |
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Examples of Proteins: | MH1 domain proteins |
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Smad family of proteins
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| Referenced in part on Cell Signaling Technology Website, Reference Section on Protein Domains. We gratefully acknowledge the following contributors: Piers Nash1, Dan Lin3, Kathleen Binns2, Clark Wells2, Rob Ingham2, Terry Kubiseski2, Bernard Liu1, Matt Smith2,3, Ivan Blasutig2,3, Maria Sierra1, Caesar Lim2,3, Michael Arc1, Jim Fawcett2 and Tony Pawson2,3.
1. Ben May Institute for Cancer Research, The University of Chicago, Chicago, Illinois, 60637, USA
2. Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, M5G 1X5, Canada
3. Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, M5S 1A8, Canada | |
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