Document Detail

Structure and Dynamics of AMPA Receptor GluA2 in Resting, Pre-Open, and Desensitized States.
MedLine Citation:
PMID:  25109876     Owner:  NLM     Status:  Publisher    
Ionotropic glutamate receptors (iGluRs) mediate the majority of fast excitatory signaling in the nervous system. Despite the profound importance of iGluRs to neurotransmission, little is known about the structures and dynamics of intact receptors in distinct functional states. Here, we elucidate the structures of the intact GluA2 AMPA receptor in an apo resting/closed state, in an activated/pre-open state bound with partial agonists and a positive allosteric modulator, and in a desensitized/closed state in complex with fluorowilliardiine. To probe the conformational properties of these states, we carried out double electron-electron resonance experiments on cysteine mutants and cryoelectron microscopy studies. We show how agonist binding modulates the conformation of the ligand-binding domain "layer" of the intact receptors and how, upon desensitization, the receptor undergoes large conformational rearrangements of the amino-terminal and ligand-binding domains. We define mechanistic principles by which to understand antagonism, activation, and desensitization in AMPA iGluRs.
Katharina L Dürr; Lei Chen; Richard A Stein; Rita De Zorzi; I Mihaela Folea; Thomas Walz; Hassane S Mchaourab; Eric Gouaux
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-8-6
Journal Detail:
Title:  Cell     Volume:  -     ISSN:  1097-4172     ISO Abbreviation:  Cell     Publication Date:  2014 Aug 
Date Detail:
Created Date:  2014-8-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0413066     Medline TA:  Cell     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014 Elsevier Inc. All rights reserved.
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