4U5D

Crystal structure of GluA2, con-ikot-ikot snail toxin, partial agonist KA and postitive modulator (R,R)-2b complex

Summary for 4U5D

• Entry DOI: 10.2210/pdb4u5d/pdb
• Descriptor: Glutamate receptor 2, Con-ikot-ikot, 3-(CARBOXYMETHYL)-4-ISOPROPENYLPROLINE, ... (5 entities in total)
• Functional Keywords: ampa receptor, transport protein-toxin complex, transport protein/toxin
• Biological source: Rattus norvegicus (Rat); More
• Total number of polymer chains: 6
• Total formula weight: 387746.71

Authors

Chen, L.,Gouaux, E. (deposition date: 2014-07-25, release date: 2014-08-13, Last modification date: 2024-10-23)

Primary citation

Chen, L.,Durr, K.L.,Gouaux, E.
X-ray structures of AMPA receptor-cone snail toxin complexes illuminate activation mechanism.
Science, 345:1021-1026, 2014

PubMed 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.

PubMed: 25103405
DOI: 10.1126/science.1258409

Experimental method

X-RAY DIFFRACTION (3.5757 Å)