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基本情報
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タイトル | CryoEM structure of a mEAK7 bound human V-ATPase complex | ||||||||||||
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機能・相同性 | ![]() proton-transporting two-sector ATPase complex / renal tubular secretion / Blockage of phagosome acidification / Ion channel transport / Regulation of MITF-M-dependent genes involved in lysosome biogenesis and autophagy / intracellular pH reduction / Nef Mediated CD8 Down-regulation / transporter activator activity / ATPase-coupled ion transmembrane transporter activity / cellular response to increased oxygen levels ...proton-transporting two-sector ATPase complex / renal tubular secretion / Blockage of phagosome acidification / Ion channel transport / Regulation of MITF-M-dependent genes involved in lysosome biogenesis and autophagy / intracellular pH reduction / Nef Mediated CD8 Down-regulation / transporter activator activity / ATPase-coupled ion transmembrane transporter activity / cellular response to increased oxygen levels / synaptic vesicle lumen acidification / endosome to plasma membrane protein transport / Golgi lumen acidification / proton-transporting V-type ATPase, V0 domain / Transferrin endocytosis and recycling / extrinsic component of synaptic vesicle membrane / plasma membrane proton-transporting V-type ATPase complex / lysosomal lumen acidification / clathrin-coated vesicle membrane / endosomal lumen acidification / vacuolar proton-transporting V-type ATPase, V0 domain / vacuolar proton-transporting V-type ATPase, V1 domain / vacuolar transport / XBP1(S) activates chaperone genes / Amino acids regulate mTORC1 / regulation of pH / proton-transporting V-type ATPase complex / ROS and RNS production in phagocytes / protein localization to cilium / Nef Mediated CD4 Down-regulation / vacuolar proton-transporting V-type ATPase complex / dendritic spine membrane / regulation of cellular pH / vacuolar acidification / osteoclast development / azurophil granule membrane / proton transmembrane transporter activity / autophagosome membrane / microvillus / tertiary granule membrane / ATPase activator activity / ficolin-1-rich granule membrane / positive regulation of Wnt signaling pathway / RHOA GTPase cycle / cilium assembly / transmembrane transporter complex / regulation of macroautophagy / specific granule membrane / enzyme regulator activity / axon terminus / ATP metabolic process / H+-transporting two-sector ATPase / proton transmembrane transport / ruffle / Insulin receptor recycling / RNA endonuclease activity / phagocytic vesicle / proton-transporting ATPase activity, rotational mechanism / endoplasmic reticulum-Golgi intermediate compartment membrane / proton-transporting ATP synthase activity, rotational mechanism / ossification / receptor-mediated endocytosis / secretory granule / brush border membrane / sensory perception of sound / transmembrane transport / synaptic vesicle membrane / small GTPase binding / cilium / endocytosis / phagocytic vesicle membrane / melanosome / apical part of cell / signaling receptor activity / ATPase binding / intracellular iron ion homeostasis / membrane => GO:0016020 / receptor-mediated endocytosis of virus by host cell / 加水分解酵素; エステル加水分解酵素 / early endosome / endosome membrane / endosome / apical plasma membrane / Golgi membrane / lysosomal membrane / intracellular membrane-bounded organelle / focal adhesion / centrosome / ubiquitin protein ligase binding / Neutrophil degranulation / protein-containing complex binding / endoplasmic reticulum membrane / ATP hydrolysis activity / extracellular exosome / nucleoplasm / ATP binding / membrane / plasma membrane / cytosol 類似検索 - 分子機能 | ||||||||||||
生物種 | ![]() ![]() | ||||||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 4.08 Å | ||||||||||||
![]() | Wang R / Li X | ||||||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Molecular basis of mEAK7-mediated human V-ATPase regulation. 著者: Rong Wang / Yu Qin / Xiao-Song Xie / Xiaochun Li / ![]() 要旨: The activity of V-ATPase is well-known to be regulated by reversible dissociation of its V and V domains in response to growth factor stimulation, nutrient sensing, and cellular differentiation. The ...The activity of V-ATPase is well-known to be regulated by reversible dissociation of its V and V domains in response to growth factor stimulation, nutrient sensing, and cellular differentiation. The molecular basis of its regulation by an endogenous modulator without affecting V-ATPase assembly remains unclear. Here, we discover that a lysosome-anchored protein termed (mammalian Enhancer-of-Akt-1-7 (mEAK7)) binds to intact V-ATPase. We determine cryo-EM structure of human mEAK7 in complex with human V-ATPase in native lipid-containing nanodiscs. The structure reveals that the TLDc domain of mEAK7 engages with subunits A, B, and E, while its C-terminal domain binds to subunit D, presumably blocking V-V torque transmission. Our functional studies suggest that mEAK7, which may act as a V-ATPase inhibitor, does not affect the activity of V-ATPase in vitro. However, overexpression of mEAK7 in HCT116 cells that stably express subunit a4 of V-ATPase represses the phosphorylation of ribosomal protein S6. Thus, this finding suggests that mEAK7 potentially links mTOR signaling with V-ATPase activity. | ||||||||||||
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文書・要旨 | ![]() | 596.8 KB | 表示 | ![]() |
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-関連構造データ
関連構造データ | ![]() 7unfMC ![]() 7uneC M: このマップから作成された原子モデル C: 同じ文献を引用 ( |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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「今月の分子」の関連する項目 |
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マップ
ファイル | ![]() | ||||||||||||||||||||
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ボクセルのサイズ | X=Y=Z: 0.842 Å | ||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
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試料の構成要素
+全体 : CryoEM structure of mEAK7 bound human V-ATPase complex
+超分子 #1: CryoEM structure of mEAK7 bound human V-ATPase complex
+分子 #1: V-type proton ATPase 116 kDa subunit a 4
+分子 #2: KIAA1609 protein, isoform CRA_a
+分子 #3: V-type proton ATPase catalytic subunit A
+分子 #4: V-type proton ATPase subunit B, brain isoform
+分子 #5: V-type proton ATPase subunit D
+分子 #6: V-type proton ATPase subunit E 1
+分子 #7: V-type proton ATPase subunit G 1
+分子 #8: V-type proton ATPase subunit F
+分子 #9: V-type proton ATPase subunit C 1
+分子 #10: V-type proton ATPase subunit H
+分子 #11: V-type proton ATPase subunit d 1
+分子 #12: V-type proton ATPase subunit e 1
+分子 #13: Ribonuclease kappa
+分子 #14: V-type proton ATPase subunit S1
+分子 #15: ATPase H(+)-transporting lysosomal accessory protein 2
+分子 #16: V-type proton ATPase 16 kDa proteolipid subunit
+分子 #17: V-type proton ATPase 21 kDa proteolipid subunit
+分子 #20: ADENOSINE-5'-DIPHOSPHATE
+分子 #21: 2-acetamido-2-deoxy-beta-D-glucopyranose
+分子 #22: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(tri...
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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試料調製
緩衝液 | pH: 7.5 |
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凍結 | 凍結剤: ETHANE |
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電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 平均電子線量: 60.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2.0 µm / 最小 デフォーカス(公称値): 1.0 µm |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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画像解析
最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 4.08 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 24984 |
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初期 角度割当 | タイプ: ANGULAR RECONSTITUTION |
最終 角度割当 | タイプ: ANGULAR RECONSTITUTION |