Structure
Volume 14, Issue 6, June 2006, Pages 1083-1092
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Article
Structure of Artemin Complexed with Its Receptor GFRα3: Convergent Recognition of Glial Cell Line-Derived Neurotrophic Factors

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Summary

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 Å crystal structure of the complex formed between ARTN and its receptor GFRα3, 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-β superfamily that reveals both conserved and specificity-determining anchor points for all GFL−GFRα 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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