PDBsum entry 1emu

Signaling protein

PDB id: 1emu

Contents

Protein chains

132 a.a. *

16 a.a. *

Ligands

GOL ×7

Waters ×61

* Residue conservation analysis

PDB id:

1emu

Name:

Signaling protein

Title:

Structure of the axin rgs-homologous domain in complex with a samp repeat from apc

Structure:

Axin. Chain: a. Fragment: rgs-homologous domain. Engineered: yes. Adenomatous polyposis coli protein. Chain: b. Fragment: third samp repeat. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: bacteria. Expression_system_taxid: 2. Synthetic: yes. Other_details: this peptide was chemically synthesized by fmoc method. The sequence of this peptide naturally occurs in humans (homo sapiens)

Biol. unit:

Dimer (from PQS)

Resolution:

1.90Å R-factor: 0.205 R-free: 0.221

Authors:

K.E.Spink,P.Polakis,W.I.Weis

Key ref:

K.E.Spink et al. (2000). Structural basis of the Axin-adenomatous polyposis coli interaction. EMBO J, 19, 2270-2279. PubMed id: 10811618 DOI: 10.1093/emboj/19.10.2270

Date:

17-Mar-00 Release date: 05-Jul-00

Protein chain

O15169  (AXIN1_HUMAN) -  Axin-1 from Homo sapiens

Seq: 862 a.a.

Struc: 132 a.a.

Protein chain

P25054  (APC_HUMAN) -  Adenomatous polyposis coli protein from Homo sapiens

Seq: 2843 a.a.

Struc: 16 a.a.

DOI no: 10.1093/emboj/19.10.2270

EMBO J 19:2270-2279 (2000)

PubMed id: 10811618

Structural basis of the Axin-adenomatous polyposis coli interaction.

K.E.Spink, P.Polakis, W.I.Weis.

ABSTRACT

Axin and the adenomatous polyposis coli (APC) tumor suppressor protein are components of the Wnt/Wingless growth factor signaling pathway. In the absence of Wnt signal, Axin and APC regulate cytoplasmic levels of the proto-oncogene beta-catenin through the formation of a large complex containing these three proteins, glycogen synthase kinase 3beta (GSK3beta) and several other proteins. Both Axin and APC are known to be critical for beta-catenin regulation, and truncations in APC that eliminate the Axin-binding site result in human cancers. A protease-resistant domain of Axin that contains the APC-binding site is a member of the regulators of G-protein signaling (RGS) superfamily. The crystal structures of this domain alone and in complex with an Axin-binding sequence from APC reveal that the Axin-APC interaction occurs at a conserved groove on a face of the protein that is distinct from the G-protein interface of classical RGS proteins. The molecular interactions observed in the Axin-APC complex provide a rationale for the evolutionary conservation seen in both proteins.

Selected figure(s)

Figure 4.
Figure 4 Structure of Axin-RGS. (A) Final Axin-RGS 2F[o] - F[c] -calc electron density map in the region of surface-exposed, conserved residues Phe156 and Gly160. The map is contoured at 1.2 . (B) Comparison of Axin-RGS with RGS4. Axin-RGS is red, RGS4 is gray. Helices are labeled as in Figure 3B. The additional helix of Axin-RGS ( 5a) and the turn of the -helix ( ) are indicated.

Figure 5.
Figure 5 Structure of the RGS–SAMP3 complex. (A) Final RGS–SAMP3 2F[o] - F[c] -calc electron density map in the region of SAMP3 residues Cys2043–Pro2049. The map is contoured at 1 . (B) The SAMP3-binding site of Axin-RGS is distinct from the G[i ]-binding site of RGS4. The Axin-RGS–SAMP3 complex is superimposed on the structure of the RGS4–G[i ]complex. Axin-RGS is red, SAMP3 is blue, RGS4 is light gray and G[i ]is dark gray. The complex is rotated 90° perpendicular to the page, then 180° around the vertical relative to the orientation of Axin-RGS in Figure 4B. (C) Conservation of the APC-binding surface of Axin-RGS. Surface representation of Axin-RGS, colored by conservation of residues within Axin family members. White indicates that a residue is not significantly conserved, yellow and orange indicate residues that are conserved or conservatively substituted, and red indicates residues that are absolutely conserved in Axin homologs. The SAMP3 peptide C[ ]trace is drawn in blue. The second conserved patch referred to in the text is visible near the top of Axin-RGS, above the SAMP3-binding site. The complex is rotated 180° around the horizontal relative to its orientation in (B).

The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2000, 19, 2270-2279) copyright 2000.

Figures were selected by an automated process.