TY - JOUR
T1 - Structure of Artemin Complexed with Its Receptor GFRα3
T2 - Convergent Recognition of Glial Cell Line-Derived Neurotrophic Factors
AU - Wang, Xinquan
AU - Baloh, Robert H.
AU - Milbrandt, Jeffrey
AU - Garcia, K. Christopher
N1 - Funding Information:
We thank N. Goriatcheva and D. Waghray for expert technical assistance, S. Juo and S. Laporte for assistance with data collection, F. Bazan for critical reading of the manuscript, S. Jain for the image of RET-GFP neurons, C. Ibanez for the gift of GFRα3 DNA, A. Bankovich for help in biophysical experiments, and M. Rickert for help in making figures. This work was supported by NIH grants AG13730 and NS39358 (J.M.), The Keck Foundation (KCG), NIH RO1 HL077325 (KCG), The Christopher Reeve Paralysis Foundation (KCG), and The Howard Hughes Medical Institute (KCG).
PY - 2006/6
Y1 - 2006/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33744789162&partnerID=8YFLogxK
U2 - 10.1016/j.str.2006.05.010
DO - 10.1016/j.str.2006.05.010
M3 - Article
C2 - 16765900
AN - SCOPUS:33744789162
SN - 0969-2126
VL - 14
SP - 1083
EP - 1092
JO - Structure
JF - Structure
IS - 6
ER -