+
データを開く
-
基本情報
登録情報 | データベース: PDB / ID: 8v88 | ||||||
---|---|---|---|---|---|---|---|
タイトル | Alpha7-nicotinic acetylcholine receptor bound to epibatidine and GAT107 | ||||||
![]() | Neuronal acetylcholine receptor subunit alpha-7,Soluble cytochrome b562 | ||||||
![]() | MEMBRANE PROTEIN / ION CHANNEL / NICOTINIC RECEPTOR | ||||||
機能・相同性 | ![]() sensory processing / dendrite arborization / response to acetylcholine / Highly calcium permeable postsynaptic nicotinic acetylcholine receptors / acetylcholine-gated channel complex / regulation of amyloid fibril formation / short-term memory / positive regulation of CoA-transferase activity / acetylcholine receptor activity / dendritic spine organization ...sensory processing / dendrite arborization / response to acetylcholine / Highly calcium permeable postsynaptic nicotinic acetylcholine receptors / acetylcholine-gated channel complex / regulation of amyloid fibril formation / short-term memory / positive regulation of CoA-transferase activity / acetylcholine receptor activity / dendritic spine organization / acetylcholine binding / chloride channel regulator activity / regulation of amyloid precursor protein catabolic process / acetylcholine receptor signaling pathway / acetylcholine-gated monoatomic cation-selective channel activity / positive regulation of amyloid-beta formation / negative regulation of amyloid-beta formation / plasma membrane raft / modulation of excitatory postsynaptic potential / positive regulation of excitatory postsynaptic potential / response to amyloid-beta / negative regulation of tumor necrosis factor production / toxic substance binding / monoatomic ion transport / monoatomic ion transmembrane transport / positive regulation of protein metabolic process / positive regulation of long-term synaptic potentiation / electron transport chain / synapse organization / response to nicotine / calcium channel activity / memory / cognition / intracellular calcium ion homeostasis / positive regulation of angiogenesis / calcium ion transport / monoatomic ion channel activity / amyloid-beta binding / postsynapse / postsynaptic membrane / positive regulation of MAPK cascade / periplasmic space / electron transfer activity / learning or memory / positive regulation of ERK1 and ERK2 cascade / response to hypoxia / neuron projection / iron ion binding / positive regulation of protein phosphorylation / synapse / heme binding / positive regulation of cell population proliferation / signal transduction / protein homodimerization activity / membrane / plasma membrane 類似検索 - 分子機能 | ||||||
生物種 | ![]() | ||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.3 Å | ||||||
![]() | Burke, S.M. / Noviello, C.M. / Hibbs, R.E. | ||||||
資金援助 | ![]()
| ||||||
![]() | ![]() タイトル: Structural mechanisms of α7 nicotinic receptor allosteric modulation and activation. 著者: Sean M Burke / Mariia Avstrikova / Colleen M Noviello / Nuriya Mukhtasimova / Jean-Pierre Changeux / Ganesh A Thakur / Steven M Sine / Marco Cecchini / Ryan E Hibbs / ![]() ![]() 要旨: The α7 nicotinic acetylcholine receptor is a pentameric ligand-gated ion channel that plays an important role in cholinergic signaling throughout the nervous system. Its unique physiological ...The α7 nicotinic acetylcholine receptor is a pentameric ligand-gated ion channel that plays an important role in cholinergic signaling throughout the nervous system. Its unique physiological characteristics and implications in neurological disorders and inflammation make it a promising but challenging therapeutic target. Positive allosteric modulators overcome limitations of traditional α7 agonists, but their potentiation mechanisms remain unclear. Here, we present high-resolution structures of α7-modulator complexes, revealing partially overlapping binding sites but varying conformational states. Structure-guided functional and computational tests suggest that differences in modulator activity arise from the stable rotation of a channel gating residue out of the pore. We extend the study using a time-resolved cryoelectron microscopy (cryo-EM) approach to reveal asymmetric state transitions for this homomeric channel and also find that a modulator with allosteric agonist activity exploits a distinct channel-gating mechanism. These results define mechanisms of α7 allosteric modulation and activation with implications across the pentameric receptor superfamily. | ||||||
履歴 |
|
-
構造の表示
構造ビューア | 分子: ![]() ![]() |
---|
-
ダウンロードとリンク
-
ダウンロード
PDBx/mmCIF形式 | ![]() | 725.2 KB | 表示 | ![]() |
---|---|---|---|---|
PDB形式 | ![]() | 617.5 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
文書・要旨 | ![]() | 2.3 MB | 表示 | ![]() |
---|---|---|---|---|
文書・詳細版 | ![]() | 2.3 MB | 表示 | |
XML形式データ | ![]() | 69.3 KB | 表示 | |
CIF形式データ | ![]() | 100.2 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 43030MC ![]() 8ut1C ![]() 8utbC ![]() 8uzjC ![]() 8v80C ![]() 8v82C ![]() 8v86C ![]() 8v89C ![]() 8v8aC ![]() 8v8cC ![]() 8v8dC C: 同じ文献を引用 ( M: このデータのモデリングに利用したマップデータ |
---|---|
類似構造データ | 類似検索 - 機能・相同性 ![]() |
-
リンク
-
集合体
登録構造単位 | ![]()
|
---|---|
1 |
|
-
要素
-タンパク質 , 1種, 5分子 ABCDE
#1: タンパク質 | 分子量: 67220.797 Da / 分子数: 5 / 由来タイプ: 組換発現 詳細: 351-353 (linker) 354-460 (SOLUBLE CYTOCHROME B562 FUSION) 551-558 (strep tag II) 559-571 (linker) 572-579 (strep tag II) 580-582 (linker) 583-599 (T2A self cleaving peptide post cleavage),351- ...詳細: 351-353 (linker) 354-460 (SOLUBLE CYTOCHROME B562 FUSION) 551-558 (strep tag II) 559-571 (linker) 572-579 (strep tag II) 580-582 (linker) 583-599 (T2A self cleaving peptide post cleavage),351-353 (linker) 354-460 (SOLUBLE CYTOCHROME B562 FUSION) 551-558 (strep tag II) 559-571 (linker) 572-579 (strep tag II) 580-582 (linker) 583-599 (T2A self cleaving peptide post cleavage),351-353 (linker) 354-460 (SOLUBLE CYTOCHROME B562 FUSION) 551-558 (strep tag II) 559-571 (linker) 572-579 (strep tag II) 580-582 (linker) 583-599 (T2A self cleaving peptide post cleavage) 由来: (組換発現) ![]() ![]() |
---|
-糖 , 3種, 15分子 ![](data/chem/img/NAG.gif)
#2: 多糖 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose #3: 多糖 | beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose #5: 糖 | ChemComp-NAG / |
---|
-非ポリマー , 6種, 130分子 ![](data/chem/img/CA.gif)
![](data/chem/img/POV.gif)
![](data/chem/img/9Z9.gif)
![](data/chem/img/EPJ.gif)
![](data/chem/img/HOH.gif)
![](data/chem/img/POV.gif)
![](data/chem/img/9Z9.gif)
![](data/chem/img/EPJ.gif)
![](data/chem/img/HOH.gif)
#4: 化合物 | ChemComp-CA / #6: 化合物 | ChemComp-POV / ( #7: 化合物 | ChemComp-9Z9 / ( #8: 化合物 | ChemComp-EPJ / #9: 化合物 | ChemComp-YLI / ( 分子量: 405.309 Da / 分子数: 5 / 由来タイプ: 合成 / 式: C18H17BrN2O2S / タイプ: SUBJECT OF INVESTIGATION #10: 水 | ChemComp-HOH / | |
---|
-詳細
研究の焦点であるリガンドがあるか | Y |
---|
-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
---|---|
EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
-
試料調製
構成要素 | 名称: Alpha7-nicotinic acetylcholine receptor bound to epibatidine and GAT107 タイプ: COMPLEX / Entity ID: #1 / 由来: RECOMBINANT |
---|---|
由来(天然) | 生物種: ![]() |
由来(組換発現) | 生物種: ![]() |
緩衝液 | pH: 7.4 |
試料 | 濃度: 7.5 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 凍結剤: ETHANE |
-
電子顕微鏡撮影
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
---|---|
顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: ![]() |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2000 nm / 最小 デフォーカス(公称値): 700 nm |
撮影 | 電子線照射量: 44 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
-
解析
EMソフトウェア |
| ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
対称性 | 点対称性: C5 (5回回転対称) | ||||||||||||||||||||||||
3次元再構成 | 解像度: 2.3 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 316844 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
|