PDBsum entry: 1mhd

Complex (transcription activator/DNA)

PDB id: 1mhd

Contents

Protein chains

123 a.a. *

DNA/RNA

Waters ×24

* Residue conservation analysis

PDB id:

1mhd

Name:

Complex (transcription activator/DNA)

Title:

Crystal structure of a smad mh1 domain bound to DNA

Structure:

DNA. Chain: c. Engineered: yes. DNA. Chain: d. Engineered: yes. Smad3. Chain: a, b. Fragment: mh1 domain, residues 1 - 144.

Source:

Synthetic: yes. Homo sapiens. Human. Organism_taxid: 9606. Cellular_location: cytoplasm. Gene: smad. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Biol. unit:

Tetramer (from PQS)

Resolution:

2.80Å R-factor: 0.212 R-free: 0.288

Authors:

Y.Shi

Key ref:

Y.Shi et al. (1998). Crystal structure of a Smad MH1 domain bound to DNA: insights on DNA binding in TGF-beta signaling. Cell, 94, 585-594. PubMed id: 9741623 DOI: 10.1016/S0092-8674(00)81600-1

Date:

18-Aug-98 Release date: 18-Aug-99

Protein chains

P84022  (SMAD3_HUMAN) -  Mothers against decapentaplegic homolog 3

Seq: 425 a.a.

Struc: 123 a.a.

 Gene Ontology (GO) functional annotation 

• Cellular component: intracellular (2 terms)
• Biological process: regulation of transcription, DNA-dependent (2 terms)
• Biochemical function: protein binding (2 terms)

DOI no: 10.1016/S0092-8674(00)81600-1

Cell 94:585-594 (1998)

PubMed id: 9741623

Crystal structure of a Smad MH1 domain bound to DNA: insights on DNA binding in TGF-beta signaling.

Y.Shi, Y.F.Wang, L.Jayaraman, H.Yang, J.Massagué, N.P.Pavletich.

ABSTRACT

The Smad family of proteins, which are frequently targeted by tumorigenic mutations in cancer, mediate TGF-beta signaling from cell membrane to nucleus. The crystal structure of a Smad3 MH1 domain bound to an optimal DNA sequence determined at 2.8 A resolution reveals a novel DNA-binding motif. In the crystals, base-specific DNA recognition is provided exclusively by a conserved 11-residue beta hairpin that is embedded in the major groove of DNA. A surface loop region, to which tumorigenic mutations map, has been identified as a functional surface important for Smad activity. This structure establishes a framework for understanding how Smad proteins may act in concert with other transcription factors in the regulation of TGF-beta-responsive genes.

Selected figure(s)

Figure 5.
Figure 5. Identification of Functional Regions by Sequence Conservation, Solvent Accessibility, and Tumorigenic Mutations(A) Mapping of the tumorigenic mutations, the invariant and solvent-exposed residues, identifies the β hairpin, the L2/L4 double loop, and the H2 basic helix as regions likely to be important for Smad functions. Color coding is the same as in Figure 2. Residues at which tumor-derived mutations occur are labeled, with corresponding mutations indicated in parentheses.(B) Close-up view showing the region with four tumorigenic mutations. Surrounding residues, which the tumorigenic residues pack against, are shown in purple.

Figure 6.
Figure 6. Comparison of DNA Recognition by β Hairpin to Known Protein–DNA Interactions that Involve β SheetsThe β hairpin of MH1 domain bound to Smad box, together with the MetJ ([35]) and Arc ( [30]) repressor–operator complexes, are schematically represented with DNA sequences and the DNA-binding motifs. Hydrogen bonds between β strand side chains and DNA bases are indicated by arrows.

The above figures are reprinted by permission from Cell Press: Cell (1998, 94, 585-594) copyright 1998.

Figures were selected by the author.