+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-30324 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
タイトル | Cryo-EM structure of human GABA(B) receptor in apo state | |||||||||
マップデータ | inactive GABAB receptor | |||||||||
試料 |
| |||||||||
キーワード | GPCR / GABA / neurosignaling / signaling protein | |||||||||
機能・相同性 | 機能・相同性情報 G protein-coupled neurotransmitter receptor activity involved in regulation of postsynaptic membrane potential / GABA B receptor activation / G protein-coupled neurotransmitter receptor activity involved in regulation of presynaptic membrane potential / G protein-coupled GABA receptor complex / negative regulation of gamma-aminobutyric acid secretion / neuron-glial cell signaling / G protein-coupled GABA receptor activity / G protein-coupled receptor heterodimeric complex / negative regulation of epinephrine secretion / negative regulation of dopamine secretion ...G protein-coupled neurotransmitter receptor activity involved in regulation of postsynaptic membrane potential / GABA B receptor activation / G protein-coupled neurotransmitter receptor activity involved in regulation of presynaptic membrane potential / G protein-coupled GABA receptor complex / negative regulation of gamma-aminobutyric acid secretion / neuron-glial cell signaling / G protein-coupled GABA receptor activity / G protein-coupled receptor heterodimeric complex / negative regulation of epinephrine secretion / negative regulation of dopamine secretion / positive regulation of growth hormone secretion / extracellular matrix protein binding / GABA receptor complex / negative regulation of adenylate cyclase activity / positive regulation of glutamate secretion / Class C/3 (Metabotropic glutamate/pheromone receptors) / synaptic transmission, GABAergic / gamma-aminobutyric acid signaling pathway / negative regulation of synaptic transmission / axolemma / GABA-ergic synapse / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / dendritic shaft / response to nicotine / mitochondrial membrane / Schaffer collateral - CA1 synapse / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / osteoblast differentiation / transmembrane signaling receptor activity / synaptic vesicle / presynaptic membrane / G alpha (i) signalling events / chemical synaptic transmission / postsynaptic membrane / response to ethanol / dendritic spine / neuron projection / protein heterodimerization activity / G protein-coupled receptor signaling pathway / negative regulation of cell population proliferation / neuronal cell body / glutamatergic synapse / endoplasmic reticulum membrane / extracellular space / plasma membrane / cytoplasm 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 7.6 Å | |||||||||
データ登録者 | Kim Y / Jeong E | |||||||||
資金援助 | 韓国, 1件
| |||||||||
引用 | ジャーナル: J Mol Biol / 年: 2020 タイトル: Structural Basis for Activation of the Heterodimeric GABA Receptor. 著者: Yoojoong Kim / Eunyoung Jeong / Ji-Hong Jeong / Youngjin Kim / Yunje Cho / 要旨: The neurotransmitter γ-aminobutyric acid (GABA) activates the metabotropic GABA receptor to generate slow, prolonged inhibitory signals that regulate the neural circuitry. The GABA receptor is an ...The neurotransmitter γ-aminobutyric acid (GABA) activates the metabotropic GABA receptor to generate slow, prolonged inhibitory signals that regulate the neural circuitry. The GABA receptor is an obligate heterodimeric G protein-coupled receptor (GPCR) comprised of GBR1 and GBR2 subunits, each with extracellular, seven-helix transmembrane (7TM), and coiled-coil domains. To understand how GABA-driven conformational changes in the extracellular domain are transmitted to the 7TM domain during signal transduction, we determined cryo-electron microscopy (EM) structures of GABA in two different states: an antagonist-bound inactive state, and an active state in which both the GABA agonist and a positive allosteric modulator (PAM) are bound. In the inactive state, the TM3 and TM5 helices in the two 7TM domains engage in cholesterol-mediated as well as direct interactions, resulting in an open conformation. GABA binding forces the extracellular domains of GBR1 and GBR2 into a compact form, relocating the linkers that connect the extracellular and 7TM domains closer to each other. The movement of the linker along with the associated extracellular loop 2 of the 7TM domain reorients the two 7TM domains and creates a new interface with the TM5, TM6 and TM7 helices in a closed conformation. PAM binding to the interface between the TM6 and TM6 helices stabilizes the active 7TM domain conformation. The relayed structural rearrangement results in significant conformational changes in the TM helices, as well as intracellular loop 3 in GBR2, which may promote the binding and activation of the Gi/o proteins. | |||||||||
履歴 |
|
-構造の表示
ムービー |
ムービービューア |
---|---|
構造ビューア | EMマップ: SurfViewMolmilJmol/JSmol |
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_30324.map.gz | 11.2 MB | EMDBマップデータ形式 | |
---|---|---|---|---|
ヘッダ (付随情報) | emd-30324-v30.xml emd-30324.xml | 12.3 KB 12.3 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_30324.png | 41.5 KB | ||
Filedesc metadata | emd-30324.cif.gz | 5.9 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-30324 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-30324 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_30324_validation.pdf.gz | 365.8 KB | 表示 | EMDB検証レポート |
---|---|---|---|---|
文書・詳細版 | emd_30324_full_validation.pdf.gz | 365.4 KB | 表示 | |
XML形式データ | emd_30324_validation.xml.gz | 6.1 KB | 表示 | |
CIF形式データ | emd_30324_validation.cif.gz | 7 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30324 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30324 | 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_30324.map.gz / 形式: CCP4 / 大きさ: 64 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
注釈 | inactive GABAB receptor | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.06 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
|
-添付データ
-試料の構成要素
-全体 : Gamma-aminobutyric acid type B receptor
全体 | 名称: Gamma-aminobutyric acid type B receptor |
---|---|
要素 |
|
-超分子 #1: Gamma-aminobutyric acid type B receptor
超分子 | 名称: Gamma-aminobutyric acid type B receptor / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all / 詳細: Inactive Gamma-aminobutyric acid type B receptor |
---|---|
由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 200 kDa/nm |
-分子 #1: Gamma-aminobutyric acid type B receptor subunit 1
分子 | 名称: Gamma-aminobutyric acid type B receptor subunit 1 / タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO |
---|---|
由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 87.248195 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: MRLLTALFAY FIVALILAFS VSAKSMSERR AVYIGALFPM SGGWPGGQAC QPAVEMALED VNSRRDILPD YELKLIHHDS KCDPGQATK YLYELLYNDP IKIILMPGCS SVSTLVAEAA RMWNLIVLSY GSSSPALSNR QRFPTFFRTH PSATLHNPTR V KLFEKWGW ...文字列: MRLLTALFAY FIVALILAFS VSAKSMSERR AVYIGALFPM SGGWPGGQAC QPAVEMALED VNSRRDILPD YELKLIHHDS KCDPGQATK YLYELLYNDP IKIILMPGCS SVSTLVAEAA RMWNLIVLSY GSSSPALSNR QRFPTFFRTH PSATLHNPTR V KLFEKWGW KKIATIQQTT EVFTSTLDDL EERVKEAGIE ITFRQSFFSD PAVPVKNLKR QDARIIVGLF YETEARKVFC EV YKERLFG KKYVWFLIGW YADNWFKIYD PSINCTVDEM TEAVEGHITT EIVMLNPANT RSISNMTSQE FVEKLTKRLK RHP EETGGF QEAPLAYDAI WALALALNKT SGGGGRSGVR LEDFNYNNQT ITDQIYRAMN SSSFEGVSGH VVFDASGSRM AWTL IEQLQ GGSYKKIGYY DSTKDDLSWS KTDKWIGGSP PADQTLVIKT FRFLSQKLFI SVSVLSSLGI VLAVVCLSFN IYNSH VRYI QNSQPNLNNL TAVGCSLALA AVFPLGLDGY HIGRNQFPFV CQARLWLLGL GFSLGYGSMF TKIWWVHTVF TKKEEK KEW RKTLEPWKLY ATVGLLVGMD VLTLAIWQIV DPLHRTIETF AKEEPKEDID VSILPQLEHC SSRKMNTWLG IFYGYKG LL LLLGIFLAYE TKSVSTEKIN DHRAVGMAIY NVAVLCLITA PVTMILSSQQ DAAFAFASLA IVFSSYITLV VLFVPKMR R LITRGEWQSE AQDTMKTGSS TNNNEEEKSR LLEKENRELE KSGRLEVLFQ UniProtKB: Gamma-aminobutyric acid type B receptor subunit 1 |
-分子 #2: Gamma-aminobutyric acid type B receptor subunit 2
分子 | 名称: Gamma-aminobutyric acid type B receptor subunit 2 / タイプ: protein_or_peptide / ID: 2 / コピー数: 1 / 光学異性体: LEVO |
---|---|
由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 92.231258 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: MASPRSSGQP GPPPPPPPPP ARLLLLLLLP LLLPLAPGAW GWARGAPRPP PSSPPLSIMG LMPLTKEVAK GSIGRGVLPA VELAIEQIR NESLLRPYFL DLRLYDTECD NAKGLKAFYD AIKYGPNHLM VFGGVCPSVT SIIAESLQGW NLVQLSFAAT T PVLADKKK ...文字列: MASPRSSGQP GPPPPPPPPP ARLLLLLLLP LLLPLAPGAW GWARGAPRPP PSSPPLSIMG LMPLTKEVAK GSIGRGVLPA VELAIEQIR NESLLRPYFL DLRLYDTECD NAKGLKAFYD AIKYGPNHLM VFGGVCPSVT SIIAESLQGW NLVQLSFAAT T PVLADKKK YPYFFRTVPS DNAVNPAILK LLKHYQWKRV GTLTQDVQRF SEVRNDLTGV LYGEDIEISD TESFSNDPCT SV KKLKGND VRIILGQFDQ NMAAKVFCCA YEENMYGSKY QWIIPGWYEP SWWEQVHTEA NSSRCLRKNL LAAMEGYIGV DFE PLSSKQ IKTISGKTPQ QYEREYNNKR SGVGPSKFHG YAYDGIWVIA KTLQRAMETL HASSRHQRIQ DFNYTDHTLG RIIL NAMNE TNFFGVTGQV VFRNGERMGT IKFTQFQDSR EVKVGEYNAV ADTLEIINDT IRFQGSEPPK DKTIILEQLR KISLP LYSI LSALTILGMI MASAFLFFNI KNRNQKLIKM SSPYMNNLII LGGMLSYASI FLFGLDGSFV SEKTFETLCT VRTWIL TVG YTTAFGAMFA KTWRVHAIFK NVKMKKKIIK DQKLLVIVGG MLLIDLCILI CWQAVDPLRR TVEKYSMEPD PAGRDIS IR PLLEHCENTH MTIWLGIVYA YKGLLMLFGC FLAWETRNVS IPALNDSKYI GMSVYNVGIM CIIGAAVSFL TRDQPNVQ F CIVALVIIFC STITLCLVFV PKLITLRTNP DAATQNRRFQ FTQNQKKEDS KTSTSVTSVN QASTSRSGRG GSENLYFQG GSGSGGDYKD DDDKDYKDDD DK UniProtKB: Gamma-aminobutyric acid type B receptor subunit 2 |
-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 | 13 mg/mL |
---|---|
緩衝液 | pH: 7.5 |
グリッド | モデル: C-flat-1.2/1.3 / 材質: COPPER / メッシュ: 400 |
凍結 | 凍結剤: ETHANE |
-電子顕微鏡法
顕微鏡 | FEI TALOS ARCTICA |
---|---|
撮影 | #0 - Image recording ID: 1 #0 - フィルム・検出器のモデル: GATAN K3 (6k x 4k) #0 - 平均電子線量: 46.545 e/Å2 / #1 - Image recording ID: 2 #1 - フィルム・検出器のモデル: GATAN K3 (6k x 4k) #1 - 平均電子線量: 46.545 e/Å2 / #2 - Image recording ID: 3 #2 - フィルム・検出器のモデル: GATAN K3 (6k x 4k) #2 - 平均電子線量: 46.545 e/Å2 |
電子線 | 加速電圧: 200 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: DIFFRACTION |
実験機器 | モデル: Talos Arctica / 画像提供: FEI Company |