+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 9b92 | ||||||||||||||||||||||||||||||
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タイトル | Cryo-EM structure of the human TRPM4 in complex with calcium at 18 degrees Celsius | ||||||||||||||||||||||||||||||
要素 | Transient receptor potential cation channel subfamily M member 4 | ||||||||||||||||||||||||||||||
キーワード | TRANSPORT PROTEIN / ion channel / TRP channel | ||||||||||||||||||||||||||||||
機能・相同性 | 機能・相同性情報 positive regulation of atrial cardiac muscle cell action potential / positive regulation of regulation of vascular associated smooth muscle cell membrane depolarization / sodium channel complex / regulation of T cell cytokine production / membrane depolarization during AV node cell action potential / membrane depolarization during bundle of His cell action potential / membrane depolarization during Purkinje myocyte cell action potential / negative regulation of bone mineralization / ligand-gated calcium channel activity / sodium ion import across plasma membrane ...positive regulation of atrial cardiac muscle cell action potential / positive regulation of regulation of vascular associated smooth muscle cell membrane depolarization / sodium channel complex / regulation of T cell cytokine production / membrane depolarization during AV node cell action potential / membrane depolarization during bundle of His cell action potential / membrane depolarization during Purkinje myocyte cell action potential / negative regulation of bone mineralization / ligand-gated calcium channel activity / sodium ion import across plasma membrane / regulation of ventricular cardiac muscle cell action potential / calcium-activated cation channel activity / inorganic cation transmembrane transport / TRP channels / dendritic cell chemotaxis / sodium channel activity / cellular response to ATP / positive regulation of heart rate / positive regulation of insulin secretion involved in cellular response to glucose stimulus / regulation of heart rate by cardiac conduction / protein sumoylation / negative regulation of osteoblast differentiation / positive regulation of fat cell differentiation / positive regulation of vasoconstriction / positive regulation of adipose tissue development / calcium ion transmembrane transport / calcium-mediated signaling / Sensory perception of sweet, bitter, and umami (glutamate) taste / positive regulation of canonical Wnt signaling pathway / positive regulation of cytosolic calcium ion concentration / protein homotetramerization / adaptive immune response / calmodulin binding / neuronal cell body / calcium ion binding / positive regulation of cell population proliferation / Golgi apparatus / endoplasmic reticulum / nucleoplasm / ATP binding / identical protein binding / membrane / plasma membrane / cytosol 類似検索 - 分子機能 | ||||||||||||||||||||||||||||||
生物種 | Homo sapiens (ヒト) | ||||||||||||||||||||||||||||||
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: 3.5 Å | ||||||||||||||||||||||||||||||
データ登録者 | Hu, J. / Lu, W. / Du, J. | ||||||||||||||||||||||||||||||
資金援助 | 米国, 9件
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引用 | ジャーナル: Nature / 年: 2024 タイトル: Physiological temperature drives TRPM4 ligand recognition and gating. 著者: Jinhong Hu / Sung Jin Park / Tyler Walter / Ian J Orozco / Garrett O'Dea / Xinyu Ye / Juan Du / Wei Lü / 要旨: Temperature profoundly affects macromolecular function, particularly in proteins with temperature sensitivity. However, its impact is often overlooked in biophysical studies that are typically ...Temperature profoundly affects macromolecular function, particularly in proteins with temperature sensitivity. However, its impact is often overlooked in biophysical studies that are typically performed at non-physiological temperatures, potentially leading to inaccurate mechanistic and pharmacological insights. Here we demonstrate temperature-dependent changes in the structure and function of TRPM4, a temperature-sensitive Ca-activated ion channel. By studying TRPM4 prepared at physiological temperature using single-particle cryo-electron microscopy, we identified a 'warm' conformation that is distinct from those observed at lower temperatures. This conformation is driven by a temperature-dependent Ca-binding site in the intracellular domain, and is essential for TRPM4 function in physiological contexts. We demonstrated that ligands, exemplified by decavanadate (a positive modulator) and ATP (an inhibitor), bind to different locations of TRPM4 at physiological temperatures than at lower temperatures, and that these sites have bona fide functional relevance. We elucidated the TRPM4 gating mechanism by capturing structural snapshots of its different functional states at physiological temperatures, revealing the channel opening that is not observed at lower temperatures. Our study provides an example of temperature-dependent ligand recognition and modulation of an ion channel, underscoring the importance of studying macromolecules at physiological temperatures. It also provides a potential molecular framework for deciphering how thermosensitive TRPM channels perceive temperature changes. | ||||||||||||||||||||||||||||||
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 | 9b92.cif.gz | 674.2 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb9b92.ent.gz | 539.8 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 9b92.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 | 9b92_validation.pdf.gz | 1.2 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 9b92_full_validation.pdf.gz | 1.2 MB | 表示 | |
XML形式データ | 9b92_validation.xml.gz | 103.5 KB | 表示 | |
CIF形式データ | 9b92_validation.cif.gz | 156.2 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/b9/9b92 ftp://data.pdbj.org/pub/pdb/validation_reports/b9/9b92 | HTTPS FTP |
-関連構造データ
関連構造データ | 44366MC 9b8wC 9b8xC 9b8yC 9b8zC 9b90C 9b91C 9b93C 9b94C M: このデータのモデリングに利用したマップデータ C: 同じ文献を引用 (文献) |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-リンク
-集合体
登録構造単位 |
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-要素
#1: タンパク質 | 分子量: 134456.484 Da / 分子数: 4 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: TRPM4, LTRPC4 / 発現宿主: Mammalia (両生類) / 参照: UniProt: Q8TD43 #2: 化合物 | ChemComp-CA / 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: human TRPM4 in complex with calcium at 18 degrees Celsius タイプ: COMPLEX / Entity ID: #1 / 由来: RECOMBINANT |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
由来(組換発現) | 生物種: Mammalia (両生類) |
緩衝液 | pH: 8 |
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: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 1900 nm / 最小 デフォーカス(公称値): 1200 nm |
撮影 | 電子線照射量: 50 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k 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: 3.5 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 301000 / 対称性のタイプ: POINT |