EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Opening of glutamate receptor channel to subconductance levels.
ジャーナル・号・ページ	Nature, Vol. 605, Issue 7908, Page 172-178, Year 2022
掲載日	2022年4月20日
著者	Maria V Yelshanskaya / Dhilon S Patel / Christopher M Kottke / Maria G Kurnikova / Alexander I Sobolevsky /
PubMed 要旨	Ionotropic glutamate receptors (iGluRs) are tetrameric ligand-gated ion channels that open their pores in response to binding of the agonist glutamate. An ionic current through a single iGluR channel ...Ionotropic glutamate receptors (iGluRs) are tetrameric ligand-gated ion channels that open their pores in response to binding of the agonist glutamate. An ionic current through a single iGluR channel shows up to four discrete conductance levels (O1-O4). Higher conductance levels have been associated with an increased number of agonist molecules bound to four individual ligand-binding domains (LBDs). Here we determine structures of a synaptic complex of AMPA-subtype iGluR and the auxiliary subunit γ2 in non-desensitizing conditions with various occupancy of the LBDs by glutamate. We show that glutamate binds to LBDs of subunits B and D only after it is already bound to at least the same number of LBDs that belong to subunits A and C. Our structures combined with single-channel recordings, molecular dynamics simulations and machine-learning analysis suggest that channel opening requires agonist binding to at least two LBDs. Conversely, agonist binding to all four LBDs does not guarantee maximal channel conductance and favours subconductance states O1 and O2, with O3 and O4 being rare and not captured structurally. The lack of subunit independence and low efficiency coupling of glutamate binding to channel opening underlie the gating of synaptic complexes to submaximal conductance levels, which provide a potential for upregulation of synaptic activity.
リンク	Nature / PubMed:35444281 / PubMed Central
手法	EM (単粒子)
解像度	3.59 - 4.74 Å
構造データ	26011 7tnj EMDB-26011, PDB-7tnj: Complex NNNN of AMPA-subtype iGluR GluA2 in complex with auxiliary subunit gamma2 (Stargazin) at low glutamate concentration (20 uM) in the presence of cyclothiazide (100 uM) 手法: EM (単粒子) / 解像度: 4.02 Å 26012 7tnk EMDB-26012, PDB-7tnk: Complex GNNN of AMPA-subtype iGluR GluA2 in complex with auxiliary subunit gamma2 (Stargazin) at low glutamate concentration (20 uM) in the presence of cyclothiazide (100 uM) 手法: EM (単粒子) / 解像度: 4.5 Å 26013 7tnl EMDB-26013, PDB-7tnl: Complex GNGN1 of AMPA-subtype iGluR GluA2 in complex with auxiliary subunit gamma2 (Stargazin) at low glutamate concentration (20 uM) in the presence of cyclothiazide (100 uM) 手法: EM (単粒子) / 解像度: 3.59 Å 26014 7tnm EMDB-26014, PDB-7tnm: Complex GNGN2 of AMPA-subtype iGluR GluA2 in complex with auxiliary subunit gamma2 (Stargazin) at low glutamate concentration (20 uM) in the presence of cyclothiazide (100 uM) 手法: EM (単粒子) / 解像度: 4.74 Å 26015 7tnn EMDB-26015, PDB-7tnn: Complex GGNN of AMPA-subtype iGluR GluA2 in complex with auxiliary subunit gamma2 (Stargazin) at low glutamate concentration (20 uM) in the presence of cyclothiazide (100 uM) 手法: EM (単粒子) / 解像度: 3.91 Å 26016 7tno EMDB-26016, PDB-7tno: Complex GGGN of AMPA-subtype iGluR GluA2 in complex with auxiliary subunit gamma2 (Stargazin) at low glutamate concentration (20 uM) in the presence of cyclothiazide (100 uM) 手法: EM (単粒子) / 解像度: 4.02 Å 26017 7tnp EMDB-26017, PDB-7tnp: Complex GGGG of AMPA-subtype iGluR GluA2 in complex with auxiliary subunit gamma2 (Stargazin) at low glutamate concentration (20 uM) in the presence of cyclothiazide (100 uM) 手法: EM (単粒子) / 解像度: 3.96 Å
化合物	ChemComp-CYZ: CYCLOTHIAZIDE / (3S)-6-クロロ-3,4-ジヒドロ-3-[(1S,4S,5S)-ビシクロ[2.2.1]ヘプタ-2-エン-5-イル](以下略) / Cyclothiazide ChemComp-GLU: GLUTAMIC ACID / グルタミン酸 / グルタミン酸
由来	rattus norvegicus (ドブネズミ)
キーワード	MEMBRANE PROTEIN (膜タンパク質) / AMPA (AMPA) / iGluR / Stargazin / cryo-EM (低温電子顕微鏡法) / complex / agonist (アゴニスト) / positive allosteric modulator (アロステリック調節因子) / subconductance level / opening / gating / glutamate (グルタミン酸)