Title : Crystal structure of the glutamate receptor
GluA1 N-terminal
domain
Abstract :
- The AMPA (α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) subfamily of iGluRs (ionotropic glutamate receptors ) is essential for fast excitatory neurotransmission in the central nervous system
- The malfunction of AMPARs ( AMPA receptors ) has been implicated in many neurological diseases, including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis
- The active channels of AMPARs and other iGluR subfamilies are tetramers formed exclusively by assembly of subunits within the same subfamily
- It has been proposed that the assembly process is controlled mainly by the extracellular ATD (N-terminal domain ) of iGluR
- In addition, ATD has also been implicated in synaptogenesis, iGluR trafficking and trans-synaptic signalling, through unknown mechanisms
- We report in the present study a 2.5 Å (1 Å=0.1 nm) resolution crystal structure of the ATD of GluA1
- Comparative analyses of the structure of GluA1- ATD and other subunits sheds light on our understanding of how ATD drives subfamily-specific assembly of AMPARs
- In addition, analysis of the crystal lattice of GluA1- ATD suggests a novel mechanism by which the ATD might participate in inter-tetramer AMPAR clustering, as well as in trans-synaptic protein-protein interactions