7QHH

Desensitized state of GluA1/2 AMPA receptor in complex with TARP-gamma 8 (TMD-LBD)

Summary for 7QHH

• Entry DOI: 10.2210/pdb7qhh/pdb
• Related: 7QHB
• EMDB information: 13969 13972 4572
• Descriptor: Isoform Flip of Glutamate receptor 1, Isoform Flip of Glutamate receptor 2, Voltage-dependent calcium channel gamma-8 subunit, ... (7 entities in total)
• Functional Keywords: glutamate, ampa receptor, tarps, membrane protein
• Biological source: Rattus norvegicus (Norway rat); More
• Total number of polymer chains: 6
• Total formula weight: 489472.63

Authors

Herguedas, B.,Kohegyi, B.,Dohrke, J.N.,Watson, J.F.,Zhang, D.,Ho, H.,Shaikh, S.,Lape, R.,Krieger, J.M.,Greger, I.H. (deposition date: 2021-12-12, release date: 2022-02-23, Last modification date: 2024-10-23)

Primary citation

Herguedas, B.,Kohegyi, B.K.,Dohrke, J.N.,Watson, J.F.,Zhang, D.,Ho, H.,Shaikh, S.A.,Lape, R.,Krieger, J.M.,Greger, I.H.
Mechanisms underlying TARP modulation of the GluA1/2-gamma 8 AMPA receptor.
Nat Commun, 13:734-734, 2022

PubMed Abstract: AMPA-type glutamate receptors (AMPARs) mediate rapid signal transmission at excitatory synapses in the brain. Glutamate binding to the receptor's ligand-binding domains (LBDs) leads to ion channel activation and desensitization. Gating kinetics shape synaptic transmission and are strongly modulated by transmembrane AMPAR regulatory proteins (TARPs) through currently incompletely resolved mechanisms. Here, electron cryo-microscopy structures of the GluA1/2 TARP-γ8 complex, in both open and desensitized states (at 3.5 Å), reveal state-selective engagement of the LBDs by the large TARP-γ8 loop ('β1'), elucidating how this TARP stabilizes specific gating states. We further show how TARPs alter channel rectification, by interacting with the pore helix of the selectivity filter. Lastly, we reveal that the Q/R-editing site couples the channel constriction at the filter entrance to the gate, and forms the major cation binding site in the conduction path. Our results provide a mechanistic framework of how TARPs modulate AMPAR gating and conductance.

PubMed: 35136046
DOI: 10.1038/s41467-022-28404-7

Experimental method

ELECTRON MICROSCOPY (3.6 Å)