PDBsum entry: 1dd1

Signaling protein

PDB id: 1dd1

Contents

Protein chains

221 a.a. *

249 a.a. *

Ligands

SO4 ×9

Waters ×302

* Residue conservation analysis

PDB id:

1dd1

Name:

Signaling protein

Title:

Crystal structure analysis of the smad4 active fragment

Structure:

Smad4. Chain: a, b, c. Fragment: smad4 active fragment

Source:

Homo sapiens. Human. Organism_taxid: 9606

Biol. unit:

Trimer (from PQS)

Resolution:

2.62Å R-factor: 0.218 R-free: 0.175

Authors:

B.Y.Qin,S.W.Lam,K.Lin

Key ref:

B.Qin et al. (1999). Crystal structure of a transcriptionally active Smad4 fragment. Structure, 7, 1493-1503. PubMed id: 10647180 DOI: 10.1016/S0969-2126(00)88340-9

Date:

05-Nov-99 Release date: 27-Nov-99

Protein chain

Q13485  (SMAD4_HUMAN) -  Mothers against decapentaplegic homolog 4

Seq: 552 a.a.

Struc: 221 a.a.

Protein chains

Q13485  (SMAD4_HUMAN) -  Mothers against decapentaplegic homolog 4

Seq: 552 a.a.

Struc: 249 a.a.

 Gene Ontology (GO) functional annotation 

• Cellular component: intracellular (1 term)
• Biological process: regulation of transcription, DNA-dependent (1 term)
• Biochemical function: protein binding (1 term)

DOI no: 10.1016/S0969-2126(00)88340-9

Structure 7:1493-1503 (1999)

PubMed id: 10647180

Crystal structure of a transcriptionally active Smad4 fragment.

B.Qin, S.S.Lam, K.Lin.

ABSTRACT

BACKGROUND: Smad4 functions as a common mediator of transforming growth factor beta (TGF-beta) signaling by forming complexes with the phosphorylated state of pathway-restricted SMAD proteins that act in specific signaling pathways to activate transcription. SMAD proteins comprise two domains, the MH1 and MH2 domain, separated by a linker region. The transcriptional activity and synergistic effect of Smad4 require a stretch of proline-rich sequence, the SMAD-activation domain (SAD), located N-terminal of the MH2 domain. To understand how the SAD contributes to Smad4 function, the crystal structure of a fragment including the SAD and MH2 domain (S4AF) was determined. RESULTS: The structure of the S4AF trimer reveals novel features important for Smad4 function. A Smad4-specific sequence insertion within the MH2 domain interacts with the C-terminal tail to form a structural extension from the core. This extension (the TOWER) contains a solvent-accessible glutamine-rich helix. The SAD reinforces the TOWER and the structural core through interactions; two residues involved in these interactions are targets of tumorigenic mutation. The solvent-accessible proline residues of the SAD are located on the same face as the glutamine-rich helix of the TOWER, forming a potential transcription activation surface. A tandem sulfate-ion-binding site was identified within the subunit interface, which may interact with the phosphorylated C-terminal sequence of pathway-restricted SMAD proteins. CONCLUSIONS: The structure suggests that the SAD provides transcriptional capability by reinforcing the structural core and coordinating with the TOWER to present the proline-rich and glutamine-rich surfaces for interaction with transcription partners. The sulfate-ion-binding sites are potential 'receptors' for the phosphorylated sequence of pathway-restricted SMAD proteins in forming a heteromeric complex. The structure thus provides a new model that can be tested using biochemical and cellular approaches.

Selected figure(s)

Figure 9.
Figure 9. Proposed model of the heteromeric interaction between Smad4 and pathway-restricted SMAD proteins. The phosphorylated C-terminal tail sequence (in ball-and-stick format) of the pathway-restricted SMAD protein adopts an extended conformation to reach the interface between two Smad4 subunits. The three monomers are shown in different colors.

The above figure is reprinted by permission from Cell Press: Structure (1999, 7, 1493-1503) copyright 1999.

Figure was selected by an automated process.