Title : Structure of
artemin complexed with its
receptor GFRalpha3 : convergent recognition of glial cell line-derived neurotrophic
factors
Abstract :
- 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