+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6nq0 | |||||||||||||||
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タイトル | Cryo-EM structure of human TPC2 channel in the ligand-bound open state | |||||||||||||||
要素 | Two pore calcium channel protein 2 | |||||||||||||||
キーワード | TRANSPORT PROTEIN / channel / lysosome | |||||||||||||||
機能・相同性 | 機能・相同性情報 endosome to lysosome transport of low-density lipoprotein particle / negative regulation of developmental pigmentation / intracellular pH reduction / intracellularly phosphatidylinositol-3,5-bisphosphate-gated monatomic cation channel activity / ligand-gated sodium channel activity / NAADP-sensitive calcium-release channel activity / regulation of exocytosis / melanosome membrane / endolysosome membrane / response to vitamin D ...endosome to lysosome transport of low-density lipoprotein particle / negative regulation of developmental pigmentation / intracellular pH reduction / intracellularly phosphatidylinositol-3,5-bisphosphate-gated monatomic cation channel activity / ligand-gated sodium channel activity / NAADP-sensitive calcium-release channel activity / regulation of exocytosis / melanosome membrane / endolysosome membrane / response to vitamin D / phosphatidylinositol-3,5-bisphosphate binding / monoatomic ion channel complex / lysosome organization / smooth muscle contraction / voltage-gated calcium channel activity / sodium ion transmembrane transport / release of sequestered calcium ion into cytosol / regulation of autophagy / calcium-mediated signaling / calcium channel activity / endocytosis involved in viral entry into host cell / Stimuli-sensing channels / intracellular calcium ion homeostasis / monoatomic ion transmembrane transport / late endosome membrane / receptor-mediated endocytosis of virus by host cell / lysosome / endosome membrane / lysosomal membrane / protein kinase binding / identical protein binding / 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: 3.7 Å | |||||||||||||||
データ登録者 | She, J. / Zeng, W. / Guo, J. / Chen, Q. / Bai, X. / Jiang, Y. | |||||||||||||||
資金援助 | 米国, 4件
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引用 | ジャーナル: Elife / 年: 2019 タイトル: Structural mechanisms of phospholipid activation of the human TPC2 channel. 著者: Ji She / Weizhong Zeng / Jiangtao Guo / Qingfeng Chen / Xiao-Chen Bai / Youxing Jiang / 要旨: Mammalian two-pore channels (TPCs) regulate the physiological functions of the endolysosome. Here we present cryo-EM structures of human TPC2 (HsTPC2), a phosphatidylinositol 3,5-bisphosphate (PI(3,5) ...Mammalian two-pore channels (TPCs) regulate the physiological functions of the endolysosome. Here we present cryo-EM structures of human TPC2 (HsTPC2), a phosphatidylinositol 3,5-bisphosphate (PI(3,5)P)-activated, Na selective channel, in the ligand-bound and apo states. The apo structure captures the closed conformation, while the ligand-bound form features the channel in both open and closed conformations. Combined with functional analysis, these structures provide insights into the mechanism of PI(3,5)P-regulated gating of TPC2, which is distinct from that of TPC1. Specifically, the endolysosome-specific PI(3,5)P binds at the first 6-TM and activates the channel - independently of the membrane potential - by inducing a structural change at the pore-lining inner helix (IS6), which forms a continuous helix in the open state but breaks into two segments at Gly317 in the closed state. Additionally, structural comparison to the voltage-dependent TPC1 structure allowed us to identify Ile551 as being responsible for the loss of voltage dependence in TPC2. | |||||||||||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 6nq0.cif.gz | 225.8 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6nq0.ent.gz | 187 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6nq0.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 | 6nq0_validation.pdf.gz | 966.3 KB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 6nq0_full_validation.pdf.gz | 975.9 KB | 表示 | |
XML形式データ | 6nq0_validation.xml.gz | 37.5 KB | 表示 | |
CIF形式データ | 6nq0_validation.cif.gz | 56.3 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/nq/6nq0 ftp://data.pdbj.org/pub/pdb/validation_reports/nq/6nq0 | 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
#1: タンパク質 | 分子量: 85671.828 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: TPCN2, TPC2 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: Q8NHX9 #2: 化合物 | |
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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: The complex of TPC2 with PI(3,5)P2 / 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: Homo sapiens (ヒト) |
緩衝液 | pH: 8 |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
試料支持 | 詳細: unspecified |
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 |
撮影 | 電子線照射量: 1.6 e/Å2 フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
-解析
ソフトウェア | 名称: PHENIX / バージョン: 1.14_3260: / 分類: 精密化 |
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CTF補正 | タイプ: NONE |
3次元再構成 | 解像度: 3.7 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 33441 / 対称性のタイプ: POINT |