+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-43783 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
タイトル | Rat GluN1-GluN2B NMDA receptor channel in complex with glutamate | |||||||||
マップデータ | The B-factor sharpened map. | |||||||||
試料 |
| |||||||||
キーワード | Ligand-gated ion channel / ionotropic glutamate receptor / synaptic membrane protein / MEMBRANE PROTEIN | |||||||||
機能・相同性 | 機能・相同性情報 neurotransmitter receptor activity involved in regulation of postsynaptic membrane potential / cellular response to curcumin / cellular response to corticosterone stimulus / cellular response to magnesium starvation / regulation of postsynaptic cytosolic calcium ion concentration / sensory organ development / sensitization / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration ...neurotransmitter receptor activity involved in regulation of postsynaptic membrane potential / cellular response to curcumin / cellular response to corticosterone stimulus / cellular response to magnesium starvation / regulation of postsynaptic cytosolic calcium ion concentration / sensory organ development / sensitization / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration / EPHB-mediated forward signaling / neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration / response to hydrogen sulfide / Assembly and cell surface presentation of NMDA receptors / olfactory learning / regulation of protein kinase A signaling / conditioned taste aversion / dendritic branch / response to other organism / regulation of respiratory gaseous exchange / protein localization to postsynaptic membrane / positive regulation of inhibitory postsynaptic potential / apical dendrite / propylene metabolic process / response to glycine / regulation of ARF protein signal transduction / fear response / response to methylmercury / positive regulation of cysteine-type endopeptidase activity / voltage-gated monoatomic cation channel activity / cellular response to dsRNA / response to carbohydrate / negative regulation of dendritic spine maintenance / regulation of monoatomic cation transmembrane transport / interleukin-1 receptor binding / cellular response to lipid / NMDA glutamate receptor activity / response to morphine / positive regulation of glutamate secretion / response to growth hormone / Synaptic adhesion-like molecules / NMDA selective glutamate receptor complex / RAF/MAP kinase cascade / parallel fiber to Purkinje cell synapse / response to manganese ion / NMDA selective glutamate receptor signaling pathway / calcium ion transmembrane import into cytosol / glutamate binding / neuromuscular process / positive regulation of reactive oxygen species biosynthetic process / protein heterotetramerization / regulation of synapse assembly / glycine binding / positive regulation of calcium ion transport into cytosol / regulation of axonogenesis / regulation of dendrite morphogenesis / male mating behavior / heterocyclic compound binding / suckling behavior / receptor clustering / startle response / behavioral response to pain / response to amine / small molecule binding / regulation of neuronal synaptic plasticity / action potential / monoatomic cation transmembrane transport / monoatomic cation transport / associative learning / positive regulation of excitatory postsynaptic potential / regulation of MAPK cascade / response to magnesium ion / social behavior / ligand-gated monoatomic ion channel activity / cellular response to organic cyclic compound / excitatory synapse / extracellularly glutamate-gated ion channel activity / cellular response to glycine / positive regulation of dendritic spine maintenance / behavioral fear response / neuron development / regulation of postsynaptic membrane potential / Unblocking of NMDA receptors, glutamate binding and activation / phosphatase binding / postsynaptic density, intracellular component / cellular response to manganese ion / glutamate receptor binding / D2 dopamine receptor binding / multicellular organismal response to stress / long-term memory / positive regulation of synaptic transmission, glutamatergic / prepulse inhibition / monoatomic cation channel activity / detection of mechanical stimulus involved in sensory perception of pain / calcium ion homeostasis / regulation of neuron apoptotic process / synaptic cleft / response to electrical stimulus / response to mechanical stimulus / glutamate-gated receptor activity 類似検索 - 分子機能 | |||||||||
生物種 | Rattus norvegicus (ドブネズミ) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.9 Å | |||||||||
データ登録者 | Chou T-H / Furukawa H | |||||||||
資金援助 | 米国, 2件
| |||||||||
引用 | ジャーナル: Nature / 年: 2024 タイトル: Molecular mechanism of ligand gating and opening of NMDA receptor. 著者: Tsung-Han Chou / Max Epstein / Russell G Fritzemeier / Nicholas S Akins / Srinu Paladugu / Elijah Z Ullman / Dennis C Liotta / Stephen F Traynelis / Hiro Furukawa / 要旨: Glutamate transmission and activation of ionotropic glutamate receptors are the fundamental means by which neurons control their excitability and neuroplasticity. The N-methyl-D-aspartate receptor ...Glutamate transmission and activation of ionotropic glutamate receptors are the fundamental means by which neurons control their excitability and neuroplasticity. The N-methyl-D-aspartate receptor (NMDAR) is unique among all ligand-gated channels, requiring two ligands-glutamate and glycine-for activation. These receptors function as heterotetrameric ion channels, with the channel opening dependent on the simultaneous binding of glycine and glutamate to the extracellular ligand-binding domains (LBDs) of the GluN1 and GluN2 subunits, respectively. The exact molecular mechanism for channel gating by the two ligands has been unclear, particularly without structures representing the open channel and apo states. Here we show that the channel gate opening requires tension in the linker connecting the LBD and transmembrane domain (TMD) and rotation of the extracellular domain relative to the TMD. Using electron cryomicroscopy, we captured the structure of the GluN1-GluN2B (GluN1-2B) NMDAR in its open state bound to a positive allosteric modulator. This process rotates and bends the pore-forming helices in GluN1 and GluN2B, altering the symmetry of the TMD channel from pseudofourfold to twofold. Structures of GluN1-2B NMDAR in apo and single-liganded states showed that binding of either glycine or glutamate alone leads to distinct GluN1-2B dimer arrangements but insufficient tension in the LBD-TMD linker for channel opening. This mechanistic framework identifies a key determinant for channel gating and a potential pharmacological strategy for modulating NMDAR activity. | |||||||||
履歴 |
|
-構造の表示
添付画像 |
---|
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_43783.map.gz | 117.8 MB | EMDBマップデータ形式 | |
---|---|---|---|---|
ヘッダ (付随情報) | emd-43783-v30.xml emd-43783.xml | 18.3 KB 18.3 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_43783.png | 63 KB | ||
Filedesc metadata | emd-43783.cif.gz | 6.9 KB | ||
その他 | emd_43783_half_map_1.map.gz emd_43783_half_map_2.map.gz | 115.7 MB 115.7 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-43783 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-43783 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
---|---|
「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_43783.map.gz / 形式: CCP4 / 大きさ: 125 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
注釈 | The B-factor sharpened map. | ||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.07 Å | ||||||||||||||||||||
密度 |
| ||||||||||||||||||||
対称性 | 空間群: 1 | ||||||||||||||||||||
詳細 | EMDB XML:
|
-添付データ
-ハーフマップ: Map A of the two half maps.
ファイル | emd_43783_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
注釈 | Map A of the two half maps. | ||||||||||||
投影像・断面図 |
| ||||||||||||
密度ヒストグラム |
-ハーフマップ: Map B of the two half maps.
ファイル | emd_43783_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
注釈 | Map B of the two half maps. | ||||||||||||
投影像・断面図 |
| ||||||||||||
密度ヒストグラム |
-試料の構成要素
-全体 : Di-heterotetrameric GluN1-GluN2B NMDA receptors
全体 | 名称: Di-heterotetrameric GluN1-GluN2B NMDA receptors |
---|---|
要素 |
|
-超分子 #1: Di-heterotetrameric GluN1-GluN2B NMDA receptors
超分子 | 名称: Di-heterotetrameric GluN1-GluN2B NMDA receptors / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#2 |
---|---|
由来(天然) | 生物種: Rattus norvegicus (ドブネズミ) |
分子量 | 理論値: 400 KDa |
-分子 #1: Isoform B of Glutamate receptor ionotropic, NMDA 1
分子 | 名称: Isoform B of Glutamate receptor ionotropic, NMDA 1 / タイプ: protein_or_peptide / ID: 1 / コピー数: 2 / 光学異性体: LEVO |
---|---|
由来(天然) | 生物種: Rattus norvegicus (ドブネズミ) |
分子量 | 理論値: 108.085633 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: MSTMHLLTFA LLFSCSFARA ASDPKIVNIG AVLSTRKHEQ MFREAVNQAN KRHGSWKIQL QATSVTHKPN AIQMALSVCE DLISSQVYA ILVSHPPTPN DHFTPTPVSY TAGFYRIPVL GLTTRMSIYS DKSIHLSFLR TVPPYSHQSS VWFEMMRVYN W NHIILLVS ...文字列: MSTMHLLTFA LLFSCSFARA ASDPKIVNIG AVLSTRKHEQ MFREAVNQAN KRHGSWKIQL QATSVTHKPN AIQMALSVCE DLISSQVYA ILVSHPPTPN DHFTPTPVSY TAGFYRIPVL GLTTRMSIYS DKSIHLSFLR TVPPYSHQSS VWFEMMRVYN W NHIILLVS DDHEGRAAQK RLETLLEERE SKSKKRNYEN LDQLSYDNKR GPKAEKVLQF DPGTKNVTAL LMEARELEAR VI ILSASED DAATVYRAAA MLDMTGSGYV WLVGEREISG NALRYAPDGI IGLQLINGKN ESAHISDAVG VVAQAVHELL EKE NITDPP RGCVGNTNIW KTGPLFKRVL MSSKYADGVT GRVEFNEDGD RKFAQYSIMN LQNRKLVQVG IYNGTHVIPN DRKI IWPGG ETEKPRGYQM STRLKIVTIH QEPFVYVKPT MSDGTCKEEF TVNGDPVKKV ICTGPNDTSP GSPRHTVPQC CYGFC IDLL IKLARTMQFT YEVHLVADGK FGTQERVQNS NKKEWNGMMG ELLSGQADMI VAPLTINNER AQYIEFSKPF KYQGLT ILV KKEIPRSTLD SFMQPFQSTL WLLVGLSVHV VAVMLYLLDR FSPFGRFKVN SQSESTDALT LSSAMWFSWG VLLNSGI GE GAPRSFSARI LGMVWAGFAM IIVASYTANL AAFLVLDRPE ERITGINDPR LRNPSDKFIY ATVKQSSVDI YFRRQVEL S TMYRHMEKHN YESAAEAIQA VRDNKLHAFI WDSAVLEFEA SQKCDLVTTG ELFFRSGFGI GMRKDSPWKQ QVSLSILKS HENGFMEDLD KTWVRYQECD SRSNAPATLT CENMAGVFML VAGGIVAGIF LIFIEIAYKR HKDARRKQMQ LAFAAVNVWR KNLQDRKSG RAEPDPKKKA TFRAITSTLA SSFKRRRSSK DTSTGGGRGA LQNQKDTVLP RRAIEREEGQ LQLCSRHRES UniProtKB: Glutamate receptor ionotropic, NMDA 1 |
-分子 #2: Glutamate receptor ionotropic, NMDA 2B
分子 | 名称: Glutamate receptor ionotropic, NMDA 2B / タイプ: protein_or_peptide / ID: 2 / コピー数: 2 / 光学異性体: LEVO |
---|---|
由来(天然) | 生物種: Rattus norvegicus (ドブネズミ) |
分子量 | 理論値: 98.845859 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: MGTMRLFLLA VLFLFSFARA TGWSHPQFEK GGGSGGGSGG SAWSHPQFEK GALVPRGRSQ KSPPSIGIAV ILVGTSDEVA IKDAHEKDD FHHLSVVPRV ELVAMNETDP KSIITRICDL MSDRKIQGVV FADDTDQEAI AQILDFISAQ TLTPILGIHG G SSMIMADK ...文字列: MGTMRLFLLA VLFLFSFARA TGWSHPQFEK GGGSGGGSGG SAWSHPQFEK GALVPRGRSQ KSPPSIGIAV ILVGTSDEVA IKDAHEKDD FHHLSVVPRV ELVAMNETDP KSIITRICDL MSDRKIQGVV FADDTDQEAI AQILDFISAQ TLTPILGIHG G SSMIMADK DESSMFFQFG PSIEQQASVM LNIMEEYDWY IFSIVTTYFP GYQDFVNKIR STIENSFVGW ELEEVLLLDM SL DDGDSKI QNQLKKLQSP IILLYCTKEE ATYIFEVANS VGLTGYGYTW IVPSLVAGDT DTVPSEFPTG LISVSYDEWD YGL PARVRD GIAIITTAAS DMLSEHSFIP EPKSSCYNTH EKRIYQSNML NRYLINVTFE GRDLSFSEDG YQMHPKLVII LLNK ERKWE RVGKWKDKSL QMKYYVWPRM CPETEEQEDD HLSIVTLEEA PFVIVESVDP LSGTCMRNTV PCQKRIISEN KTDEE PGYI KKCCKGFCID ILKKISKSVK FTYDLYLVTN GKHGKKINGT WNGMIGEVVM KRAYMAVGSL TINEERSEVV DFSVPF IET GISVMVSRSN GTVSPSAFLE PFSACVWVMM FVMLLIVSAV AVFVFEYFSP VGYNRSLADG REPGGPSFTI GKAIWLL WG LVFNNSVPVQ NPKGTTSKIM VSVWAFFAVI FLASYTANLA AFMIQEEYVD QVSGLSDKKF QRPNDFSPPF RFGTVPNG S TERNIRNNYA EMHAYMGKFN QRGVDDALLS LKTGKLDAFI YDAAVLNYMA GRDEGCKLVT IGSGKVFAST GYGIAIQKD SGWKRQVDLA ILQLFGDGEM EELEALWLTG ICHNEKNEVM SSQLDIDNMA GVFYMLGAAM ALSLITFISE HLFYWQFRHS FMG UniProtKB: Glutamate receptor ionotropic, NMDA 2B |
-分子 #3: GLUTAMIC ACID
分子 | 名称: GLUTAMIC ACID / タイプ: ligand / ID: 3 / コピー数: 2 / 式: GLU |
---|---|
分子量 | 理論値: 147.129 Da |
Chemical component information | ChemComp-GLU: |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
---|---|
解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
濃度 | 4 mg/mL |
---|---|
緩衝液 | pH: 7.5 |
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 85 % / チャンバー内温度: 285 K / 装置: FEI VITROBOT MARK IV |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
---|---|
撮影 | フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 平均電子線量: 58.8 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD 最大 デフォーカス(公称値): 2.8000000000000003 µm 最小 デフォーカス(公称値): 1.6 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
初期モデル | モデルのタイプ: NONE |
---|---|
最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.9 Å / 解像度の算出法: FSC 0.143 CUT-OFF / ソフトウェア - 名称: cryoSPARC / 使用した粒子像数: 230178 |
初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD / ソフトウェア - 名称: cryoSPARC |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD / ソフトウェア - 名称: cryoSPARC |