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PDBsum entry 1emu
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Signaling protein
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PDB id
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1emu
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Structural basis of the axin-Adenomatous polyposis coli interaction.
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Authors
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K.E.Spink,
P.Polakis,
W.I.Weis.
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Ref.
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EMBO J, 2000,
19,
2270-2279.
[DOI no: ]
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PubMed id
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Abstract
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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.
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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.
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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).
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The above figures are
reprinted
from an Open Access publication published by Macmillan Publishers Ltd:
EMBO J
(2000,
19,
2270-2279)
copyright 2000.
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