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    Simultaneous recording from four lipid bilayers

2021 - Structure and desensitization of AMPA receptor complexes with type II TARP γ5 and GSG1L

Icon Orbit Mini  Orbit Mini Publication in Molecular Cell (2021)

Authors:
Klykov O., Gangwar S. P., Yelshanskaya M. V., Laura Yen., Sobolevsky A. I.

Journal:
Orbit Mini Publication in Molecular Cell (2021) doi:10.1016/j.molcel.2021.09.030


Abstract: 

AMPA receptors (AMPARs) mediate the majority of excitatory neurotransmission. Their surface expression, trafficking, gating, and pharmacology are regulated by auxiliary subunits. Of the two types of TARP auxiliary subunits, type I TARPs assume activating roles, while type II TARPs serve suppressive functions. We present cryo-EM structures of GluA2 AMPAR in complex with type II TARP γ5, which reduces steady-state currents, increases single-channel conductance, and slows recovery from desensitization. Regulation of AMPAR function depends on its ligand-binding domain (LBD) interaction with the γ5 head domain. GluA2-γ5 complex shows maximum stoichiometry of two TARPs per AMPAR tetramer, being different from type I TARPs but reminiscent of the auxiliary subunit GSG1L. Desensitization of both GluA2-GSG1L and GluA2-γ5 complexes is accompanied by rupture of LBD dimer interface, while GluA2-γ5 but not GluA2-GSG1L LBD dimers remain two-fold symmetric. Different structural architectures and desensitization mechanisms of complexes with auxiliary subunits endow AMPARs with broad functional capabilities.


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