Structural basis of ligand binding in plant glutamate receptor homologues

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In the nervous systems of animals, ionotropic glutamate receptors mediate chemical communication between nerve cells. Plants lack a nervous system, but possess proteins homologous to glutamate receptors, which have been implicated in root development, ion transport, signalling, and metabolism. Until recently, nobody had been able to functionally characterise any of these plant glutamate receptor homologues. I now showed for one of the twenty subunits from Arabidopsis thaliana – AtGLR1.4 – that it forms a ligand-gated cation channel just like the animal glutamate receptor subunits. However, this receptor does not sense glutamate but a number of different amino acids, some acting as agonists, some as antagonists with varying efficacies. The aim of the proposed project is to elucidate the structural basis of this novel, unusually broad ligand selectivity of AtGLR1.4. To this end, a soluble form of the At-GLR1.4 ligand binding domain will be constructed, expressed, and purified on a large scale. The soluble ligand binding domain will then be characterised and crystallised in complex with different amino acid ligands to obtain X-ray structures. These structures will provide insight into the interactions responsible for the broad ligand selectivity as well as into the mechanism of receptor activation.