The glutamate receptor ion channels which mediate excitatory synaptic transmission in the mammalian brain have a unique architecture distinct from that for other ligand gated ion channels. Ten years ago the 1st crystal structure was solved for an AMPA receptor ligand binding domain1, with members of other iGluR gene families following over the next few years2-4. The ligand binding domain is preceded by a large amino terminal domain which controls assembly, but which does not bind neurotransmitter. Despite its key biological role structures of the ATD have not been solved. A major impediment to this is the poor expression of iGluR ATDs in Escherichia coli. To address this we screened ATD expression in HEK cells using constructs designed for secretion of soluble proteins and focused on the GluR6 subtype for which we can obtain 4 mg/l of glycosylated protein. The results of crystallization screens and data collection with synchrotron radiation indicate that it will be possible to solve a structure of the GluR6 ATD and explore its role in subtype specific assembly.1. Armstrong, N., Sun, Y., Chen, G.Q. & Gouaux, E. Structure of a glutamate-receptor ligand-binding core in complex with kainate. Nature 395, 913-917 (1998).2. Furukawa, H., Singh, S.K., Mancusso, R. & Gouaux, E. Subunit arrangement and function in NMDA receptors. Nature 438, 185-192 (2005).3. Mayer, M.L. Crystal Structures of the GluR5 and GluR6 Ligand Binding Cores: Molecular Mechanisms Underlying Kainate Receptor Selectivity. Neuron 45, 539-552 (2005).4. Yao, Y., Harrison, C.B., Freddolino, P.L., Schulten, K. & Mayer, M.L. Molecular mechanism of ligand recognition by NR3 subtype glutamate receptors. Embo J 27, 2158-70 (2008).