000120929 001__ 120929
000120929 005__ 20240319081005.0
000120929 0247_ $$2doi$$a10.1038/s41467-022-28404-7
000120929 0248_ $$2sideral$$a131237
000120929 037__ $$aART-2022-131237
000120929 041__ $$aeng
000120929 100__ $$0(orcid)0000-0003-2044-4795$$aHerguedas, Beatriz$$uUniversidad de Zaragoza
000120929 245__ $$aMechanisms underlying TARP modulation of the GluA1/2-y8 AMPA receptor
000120929 260__ $$c2022
000120929 5060_ $$aAccess copy available to the general public$$fUnrestricted
000120929 5203_ $$aAMPA-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.
000120929 536__ $$9info:eu-repo/grantAgreement/ES/MCINN/AEI/RYC2018-025720-I$$9info:eu-repo/grantAgreement/ES/MICINN-AEI/PID2019-106284GA-I00
000120929 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000120929 590__ $$a16.6$$b2022
000120929 592__ $$a5.116$$b2022
000120929 591__ $$aMULTIDISCIPLINARY SCIENCES$$b6 / 73 = 0.082$$c2022$$dQ1$$eT1
000120929 593__ $$aBiochemistry, Genetics and Molecular Biology (miscellaneous)$$c2022$$dQ1
000120929 593__ $$aPhysics and Astronomy (miscellaneous)$$c2022$$dQ1
000120929 593__ $$aChemistry (miscellaneous)$$c2022$$dQ1
000120929 594__ $$a24.9$$b2022
000120929 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000120929 700__ $$aKohegyi, Bianka K.
000120929 700__ $$aDohrke, Jan-Niklas
000120929 700__ $$aWatson, Jake F.
000120929 700__ $$aZhang, Danyang
000120929 700__ $$aHo, Hinze
000120929 700__ $$aShaikh, Saher A.
000120929 700__ $$aLape, Remigijus
000120929 700__ $$aKrieger, James M.
000120929 700__ $$aGreger, Ingo H.
000120929 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000120929 773__ $$g13, 734 (2022), 13$$tNature communications$$x2041-1723
000120929 8564_ $$s2625540$$uhttps://zaguan.unizar.es/record/120929/files/texto_completo.pdf$$yVersión publicada
000120929 8564_ $$s1480206$$uhttps://zaguan.unizar.es/record/120929/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000120929 909CO $$ooai:zaguan.unizar.es:120929$$particulos$$pdriver
000120929 951__ $$a2024-03-18-14:34:36
000120929 980__ $$aARTICLE