PMID: 21317871

 

    Legend: Sugar

Title : Dynamics and allosteric potential of the AMPA receptor N-terminal domain

Abstract :

1. Glutamate-gated ion channels (ionotropic glutamate receptors , i GluRs ) sense the extracellular milieu via an extensive extracellular portion, comprised of two clamshell-shaped segments
2. The distal, N-terminal domain (NTD) has allosteric potential in NMDA-type iGluRs , which has not been ascribed to the analogous domain in AMPA receptors ( AMPARs )
3. In this study, we present new structural data uncovering dynamic properties of the GluA2 and GluA3 AMPAR NTDs
4. GluA3 features a zipped-open dimer interface with unconstrained lower clamshell lobes , reminiscent of metabotropic GluRs ( mGluRs )
5. The resulting labile interface supports interprotomer rotations, which can be transmitted to downstream receptor segments
6. Normal mode analysis reveals two dominant mechanisms of AMPAR NTD motion: intraprotomer clamshell motions and interprotomer counter-rotations, as well as accessible interconversion between AMPAR and mGluR conformations
7. In addition, we detect electron density for a potential ligand in the GluA2 interlobe cleft, which may trigger lobe motions
8. Together, these data support a dynamic role for the AMPAR NTDs, which widens the allosteric landscape of the receptor and could provide a novel target for ligand development