Researchers have for the first time obtained a high-resolution structure of a three-molecule receptor-ligand complex that could help shed light on neurodegenerative diseases such as Parkinson's. The complex includes two receptor molecules, called GFRa3, bound with its ligand, artemin, which fit together like a lock and key. These molecules play a key role in chemical signal transmission and in the development and health of neurons.

This research was the result of macromolecular crystallography data measured at SSRL BL11-1 and at the Advanced Light Source in Berkeley. Researchers collected x-ray diffraction data from two types of crystals- the artemin-GFRa3 bound complex, and artemin by itself - overcoming the inherent difficulty of growing receptor molecules such as GFRa3 to into crystals.

Glia are important nervous system cells that help regulate the internal environment in the brain. Artemin is one of four compounds belonging to a family of ligands known as glial cell line-derived neurotrophic factor (GDNF), which are responsible for maintaining the health of dopaminergic and motorneurons. Other ligands in this family include GDNF itself, neurturin, and persephin. GDNF and its receptor GFRa1 have been linked to neurodegenerative diseases such as Parkinson's disease, but have so far defied crystallization. The artemin-GFRa3 complex is structurally similar to GDNF-GFRa1, and therefore determining the structure of this related complex could lead to the development of new therapies for neurodegenerative diseases.

To learn more about this research see the full scientific highlight at:
http://www-ssrl.slac.stanford.edu/research/highlights_archive/ARTN.html

Wang, X., Baloh, R.H., Milbrandt, J., and Garcia, K.C. (2006). Structure of Artemin Complexed with Its Receptor GFRa3: Convergent Recognition of Glial Cell Line-Derived Neurotrophic Factors. Structure 14, 1083-1092.