+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 9awj | ||||||
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タイトル | Bovine adult muscle nAChR bound to ACh | ||||||
要素 | (Acetylcholine receptor subunit ...) x 4 | ||||||
キーワード | MEMBRANE PROTEIN / Bovine muscle nicotinic acetylcholine receptor | ||||||
機能・相同性 | 機能・相同性情報 Highly sodium permeable postsynaptic acetylcholine nicotinic receptors / Highly calcium permeable postsynaptic nicotinic acetylcholine receptors / Highly calcium permeable nicotinic acetylcholine receptors / postsynaptic membrane organization / skeletal muscle tissue growth / musculoskeletal movement / acetylcholine receptor activity / neuromuscular synaptic transmission / acetylcholine-gated channel complex / behavioral response to nicotine ...Highly sodium permeable postsynaptic acetylcholine nicotinic receptors / Highly calcium permeable postsynaptic nicotinic acetylcholine receptors / Highly calcium permeable nicotinic acetylcholine receptors / postsynaptic membrane organization / skeletal muscle tissue growth / musculoskeletal movement / acetylcholine receptor activity / neuromuscular synaptic transmission / acetylcholine-gated channel complex / behavioral response to nicotine / acetylcholine-gated monoatomic cation-selective channel activity / muscle cell development / nervous system process / acetylcholine binding / synaptic transmission, cholinergic / acetylcholine receptor signaling pathway / postsynaptic specialization membrane / neuromuscular junction development / muscle cell cellular homeostasis / monoatomic cation transport / membrane depolarization / skeletal muscle contraction / neuronal action potential / muscle contraction / response to nicotine / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / neuromuscular junction / neuron cellular homeostasis / channel activity / postsynaptic membrane / neuron projection / synapse / cell surface / signal transduction / plasma membrane 類似検索 - 分子機能 | ||||||
生物種 | Bos taurus (ウシ) | ||||||
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: 2.45 Å | ||||||
データ登録者 | Li, H. / Hibbs, R.E. | ||||||
資金援助 | 米国, 1件
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引用 | ジャーナル: Nature / 年: 2024 タイトル: Structural switch in acetylcholine receptors in developing muscle. 著者: Huanhuan Li / Jinfeng Teng / Ryan E Hibbs / 要旨: During development, motor neurons originating in the brainstem and spinal cord form elaborate synapses with skeletal muscle fibres. These neurons release acetylcholine (ACh), which binds to nicotinic ...During development, motor neurons originating in the brainstem and spinal cord form elaborate synapses with skeletal muscle fibres. These neurons release acetylcholine (ACh), which binds to nicotinic ACh receptors (AChRs) on the muscle, initiating contraction. Two types of AChR are present in developing muscle cells, and their differential expression serves as a hallmark of neuromuscular synapse maturation. The structural principles underlying the switch from fetal to adult muscle receptors are unknown. Here, we present high-resolution structures of both fetal and adult muscle nicotinic AChRs, isolated from bovine skeletal muscle in developmental transition. These structures, obtained in the absence and presence of ACh, provide a structural context for understanding how fetal versus adult receptor isoforms are tuned for synapse development versus the all-or-none signalling required for high-fidelity skeletal muscle contraction. We find that ACh affinity differences are driven by binding site access, channel conductance is tuned by widespread surface electrostatics and open duration changes result from intrasubunit interactions and structural flexibility. The structures further reveal pathogenic mechanisms underlying congenital myasthenic syndromes. | ||||||
履歴 |
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-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 9awj.cif.gz | 772.4 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb9awj.ent.gz | 652.8 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 9awj.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
文書・要旨 | 9awj_validation.pdf.gz | 1.7 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 9awj_full_validation.pdf.gz | 1.7 MB | 表示 | |
XML形式データ | 9awj_validation.xml.gz | 72.1 KB | 表示 | |
CIF形式データ | 9awj_validation.cif.gz | 109 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/aw/9awj ftp://data.pdbj.org/pub/pdb/validation_reports/aw/9awj | HTTPS FTP |
-関連構造データ
-リンク
-集合体
登録構造単位 |
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1 |
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-要素
-Acetylcholine receptor subunit ... , 4種, 5分子 ACEDB
#1: タンパク質 | 分子量: 49949.828 Da / 分子数: 2 / 由来タイプ: 天然 / 由来: (天然) Bos taurus (ウシ) / 参照: UniProt: P02709 #2: タンパク質 | | 分子量: 55111.832 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Bos taurus (ウシ) / 参照: UniProt: P04758 #3: タンパク質 | | 分子量: 56543.926 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Bos taurus (ウシ) / 参照: UniProt: P04759 #4: タンパク質 | | 分子量: 52613.262 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Bos taurus (ウシ) / 参照: UniProt: P02715 |
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-糖 , 6種, 7分子
#5: 多糖 | alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-2)-alpha-D- ...alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose タイプ: oligosaccharide / 分子量: 1721.527 Da / 分子数: 1 / 由来タイプ: 組換発現 | ||
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#6: 多糖 | alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1- ...alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | ||
#7: 多糖 | alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]alpha-D- ...alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | ||
#8: 多糖 | alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-3)-alpha-D- ...alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | ||
#9: 多糖 | #10: 多糖 | alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2- ...alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | |
-非ポリマー , 3種, 9分子
#11: 化合物 | #12: 化合物 | #13: 水 | ChemComp-HOH / | |
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-詳細
研究の焦点であるリガンドがあるか | Y |
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-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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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: Bovine muscle nicotinic acetylcholine receptor / タイプ: COMPLEX / Entity ID: #1-#4 / 由来: NATURAL |
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分子量 | 実験値: NO |
由来(天然) | 生物種: Bos taurus (ウシ) |
緩衝液 | pH: 7.4 |
試料 | 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 |
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顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: OTHER |
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): 1600 nm |
撮影 | 電子線照射量: 50 e/Å2 フィルム・検出器のモデル: FEI FALCON III (4k x 4k) |
-解析
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3次元再構成 | 解像度: 2.45 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 167900 / 対称性のタイプ: POINT |
原子モデル構築 | プロトコル: AB INITIO MODEL / 空間: REAL |
原子モデル構築 | 詳細: cryosparc ab initial model / Source name: Other / タイプ: experimental model |