PDBsum entry 1khx

Transcription

PDB id: 1khx

Contents

Protein chain

203 a.a. *

Waters ×144

* Residue conservation analysis

PDB id:

1khx

Name:

Transcription

Title:

Crystal structure of a phosphorylated smad2

Structure:

Smad2. Chain: a. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562

Biol. unit:

Trimer (from PDB file)

Resolution:

1.80Å R-factor: 0.215 R-free: 0.241

Authors:

J.-W.Wu,M.Hu,J.Chai,J.Seoane,M.Huse,S.Kyin,T.W.Muir,R.Fairman, J.Massague,Y.Shi

Key ref:

J.W.Wu et al. (2001). Crystal structure of a phosphorylated Smad2. Recognition of phosphoserine by the MH2 domain and insights on Smad function in TGF-beta signaling. Mol Cell, 8, 1277-1289. PubMed id: 11779503 DOI: 10.1016/S1097-2765(01)00421-X

Date:

01-Dec-01 Release date: 06-Feb-02

Protein chain

Q15796  (SMAD2_HUMAN) -  Mothers against decapentaplegic homolog 2 from Homo sapiens

Seq: 467 a.a.

Struc: 203 a.a.

DOI no: 10.1016/S1097-2765(01)00421-X

Mol Cell 8:1277-1289 (2001)

PubMed id: 11779503

Crystal structure of a phosphorylated Smad2. Recognition of phosphoserine by the MH2 domain and insights on Smad function in TGF-beta signaling.

J.W.Wu, M.Hu, J.Chai, J.Seoane, M.Huse, C.Li, D.J.Rigotti, S.Kyin, T.W.Muir, R.Fairman, J.Massagué, Y.Shi.

ABSTRACT

Ligand-induced phosphorylation of the receptor-regulated Smads (R-Smads) is essential in the receptor Ser/Thr kinase-mediated TGF-beta signaling. The crystal structure of a phosphorylated Smad2, at 1.8 A resolution, reveals the formation of a homotrimer mediated by the C-terminal phosphoserine (pSer) residues. The pSer binding surface on the MH2 domain, frequently targeted for inactivation in cancers, is highly conserved among the Co- and R-Smads. This finding, together with mutagenesis data, pinpoints a functional interface between Smad2 and Smad4. In addition, the pSer binding surface on the MH2 domain coincides with the surface on R-Smads that is required for docking interactions with the serine-phosphorylated receptor kinases. These observations define a bifunctional role for the MH2 domain as a pSer-X-pSer binding module in receptor Ser/Thr kinase signaling pathways.

Selected figure(s)

Figure 4.
Figure 4. A Close-Up View of the Interactions between the Phosphorylated C Terminus from One Monomer and the Loop-Strand Pocket of the Adjacent Monomer(A) An electron density map of the phosphorylated C terminus. The 2F[o]-F[c] map (omit map), shown in pink, was contoured at 1.5σ and was calculated by simulated annealing using CNS (Brunger et al., 1998) with the omission of the C-terminal five residues. The backbone as well as the side chains of four residues are shown in yellow.(B) An overall view of the interactions. The C terminus is shown as a yellow coil, while its binding partner is represented as a transparent surface with backbones in pink. The side chains of the last five residues in the C terminus (CSSMS) and the basic residues in the loop-strand pocket are shown.(C) A stereo view of hydrogen bond networks. The two interacting monomers are shown in green and blue, respectively. Their side chains are colored gold and yellow. Hydrogen bonds among oxygen (red) and nitrogen (blue) atoms and water molecules (red) are indicated by red dashed lines.(D) A stereo view of the van der Waals contacts between the phosphorylated C terminus from one monomer and the loop-strand pocket of the adjacent monomer. The coloring scheme is the same as in (C).

Figure 6.
Figure 6. Implications for RSK-Mediated Signaling(A) Proposed mechanisms of Smad2 dissociation from the receptor kinase (TβRI) (Huse et al., 1999) after phosphorylation. The positively charged loop-strand pocket on Smad2, which is responsible for binding the phosphorylated C terminus of another Smad2, coincides with the L3 loop region, which is involved in interactions with the L45 loop and the GS region of the receptor kinase. The mutual exclusion is proposed to lead to dissociation of phosphorylated Smad2 from the receptors.(B) A schematic diagram of signal flow in the RSK-mediated signaling, highlighting the MH2 domain as the pSer binding motif.

The above figures are reprinted by permission from Cell Press: Mol Cell (2001, 8, 1277-1289) copyright 2001.

Figures were selected by an automated process.