IMIS | Flanders Marine Institute
 

Flanders Marine Institute

Platform for marine research

IMIS

Publications | Institutes | Persons | Datasets | Projects | Maps
[ report an error in this record ]basket (0): add | show Printer-friendly version

X-ray structures of AMPA receptor–cone snail toxin complexes illuminate activation mechanism
Chen, L.; Dürr, K.L.; Gouaux, E. (2014). X-ray structures of AMPA receptor–cone snail toxin complexes illuminate activation mechanism. Science (Wash.) 345(6200): 1021-1026 . hdl.handle.net/10.1126/science.1258409
In: Science (Washington). American Association for the Advancement of Science: New York, N.Y. ISSN 0036-8075, more
Peer reviewed article  

Available in  Authors 

Keyword
    Marine

Authors  Top 
  • Chen, L.
  • Dürr, K.L.
  • Gouaux, E.

Abstract
    AMPA-sensitive glutamate receptors are crucial to the structural and dynamic properties of the brain, to the development and function of the central nervous system, and to the treatment of neurological conditions from depression to cognitive impairment. However, the molecular principles underlying AMPA receptor activation have remained elusive. We determined multiple x-ray crystal structures of the GluA2 AMPA receptor in complex with a Conus striatus cone snail toxin, a positive allosteric modulator, and orthosteric agonists, at 3.8 to 4.1 angstrom resolution. We show how the toxin acts like a straightjacket on the ligand-binding domain (LBD) “gating ring,” restraining the domains via both intra- and interdimer cross-links such that agonist-induced closure of the LBD “clamshells” is transduced into an irislike expansion of the gating ring. By structural analysis of activation-enhancing mutants, we show how the expansion of the LBD gating ring results in pulling forces on the M3 helices that, in turn, are coupled to ion channel gating.

All data in IMIS is subject to the VLIZ privacy policy Top | Authors