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PDBsum entry 2gh0
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Hormone/growth factor
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PDB id
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2gh0
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References listed in PDB file
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Key reference
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Title
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Structure of artemin complexed with its receptor gfralpha3: convergent recognition of glial cell line-Derived neurotrophic factors.
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Authors
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X.Wang,
R.H.Baloh,
J.Milbrandt,
K.C.Garcia.
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Ref.
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Structure, 2006,
14,
1083-1092.
[DOI no: ]
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PubMed id
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Abstract
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Artemin (ARTN) is a member of the glial cell line-derived neurotrophic factor
(GDNF) family ligands (GFLs) which regulate the development and maintenance of
many neuronal populations in the mammalian nervous system. Here we report the
1.92 A crystal structure of the complex formed between ARTN and its receptor
GFRalpha3, which is the initiating step in the formation of a ternary signaling
complex containing the shared RET receptor. It represents a new receptor-ligand
interaction mode for the TGF-beta superfamily that reveals both conserved and
specificity-determining anchor points for all GFL-GFRalpha pairs. In tandem with
the complex structure, cellular studies using receptor chimeras implicate
dyad-symmetric composite interfaces for recruitment and dimerization of RET,
leading to intracellular signaling. These studies should facilitate the
functional dissection of the specific versus pleiotropic roles of this system in
neurobiology, as well as its exploitation for therapeutic applications.
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Figure 3.
Figure 3. Ligand-Receptor Contacts between Artemin and
GFRa3
(A) Molecular surfaces highlight the knob-in-hole
complementarity between the protruding ARTN finger region (cyan)
and the recessed center of a triangular spiral of a helices in
GFRa3 D2 (deep salmon) formed by helices a1, a2, and a5.
(B) Interatomic contacts between ARTN and GFRa3, with the
hydrophobic core of ARTN surrounded by a halo of polar
interactions.
(C) Electrostatic footprints and
complementarity of buried residues of ARTN on top of the GFRa3
surface.
(D) Electrostatic footprints and complementarity
of buried residues of GFRa3 on top of the ARTN surface.
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The above figure is
reprinted
by permission from Cell Press:
Structure
(2006,
14,
1083-1092)
copyright 2006.
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