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基本情報
登録情報 | データベース: EMDB / ID: EMD-25780 | |||||||||
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タイトル | Cryo-EM structure of archazolid A bound to yeast VO V-ATPase | |||||||||
![]() | Yeast VO motor with Archazolid A | |||||||||
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機能・相同性 | ![]() cell wall mannoprotein biosynthetic process / ATPase-coupled ion transmembrane transporter activity / protein localization to vacuolar membrane / cellular response to alkaline pH / Insulin receptor recycling / Transferrin endocytosis and recycling / polyphosphate metabolic process / ROS and RNS production in phagocytes / Amino acids regulate mTORC1 / Golgi lumen acidification ...cell wall mannoprotein biosynthetic process / ATPase-coupled ion transmembrane transporter activity / protein localization to vacuolar membrane / cellular response to alkaline pH / Insulin receptor recycling / Transferrin endocytosis and recycling / polyphosphate metabolic process / ROS and RNS production in phagocytes / Amino acids regulate mTORC1 / Golgi lumen acidification / P-type proton-exporting transporter activity / endosomal lumen acidification / vacuolar proton-transporting V-type ATPase, V0 domain / vacuolar transport / protein targeting to vacuole / vacuole organization / proton-transporting V-type ATPase complex / fungal-type vacuole / cellular hyperosmotic response / vacuolar proton-transporting V-type ATPase complex / phosphatidylinositol-3,5-bisphosphate binding / vacuolar acidification / fungal-type vacuole membrane / proton transmembrane transporter activity / intracellular copper ion homeostasis / Neutrophil degranulation / RNA endonuclease activity / proton-transporting ATPase activity, rotational mechanism / proton transmembrane transport / cell periphery / transmembrane transport / endocytosis / ATPase binding / protein-containing complex assembly / intracellular iron ion homeostasis / membrane raft / Golgi membrane / endoplasmic reticulum membrane / membrane 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: 2.8 Å | |||||||||
![]() | Keon KA / Rubinstein JL / Benlekbir S / Kirsch SH / Muller R | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Cryo-EM of the Yeast V Complex Reveals Distinct Binding Sites for Macrolide V-ATPase Inhibitors. 著者: Kristine A Keon / Samir Benlekbir / Susanne H Kirsch / Rolf Müller / John L Rubinstein / ![]() ![]() 要旨: Vacuolar-type adenosine triphosphatases (V-ATPases) are proton pumps found in almost all eukaryotic cells. These enzymes consist of a soluble catalytic V region that hydrolyzes ATP and a membrane- ...Vacuolar-type adenosine triphosphatases (V-ATPases) are proton pumps found in almost all eukaryotic cells. These enzymes consist of a soluble catalytic V region that hydrolyzes ATP and a membrane-embedded V region responsible for proton translocation. V-ATPase activity leads to acidification of endosomes, phagosomes, lysosomes, secretory vesicles, and the trans-Golgi network, with extracellular acidification occurring in some specialized cells. Small-molecule inhibitors of V-ATPase have played a crucial role in elucidating numerous aspects of cell biology by blocking acidification of intracellular compartments, while therapeutic use of V-ATPase inhibitors has been proposed for the treatment of cancer, osteoporosis, and some infections. Here, we determine structures of the isolated V complex from bound to two well-known macrolide inhibitors: bafilomycin A1 and archazolid A. The structures reveal different binding sites for the inhibitors on the surface of the proton-carrying c ring, with only a small amount of overlap between the two sites. Binding of both inhibitors is mediated primarily through van der Waals interactions in shallow pockets and suggests that the inhibitors block rotation of the ring. Together, these structures indicate the existence of a large chemical space available for V-ATPase inhibitors that block acidification by binding the c ring. | |||||||||
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画像 | ![]() | 79.3 KB | ||
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注釈 | Yeast VO motor with Archazolid A | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.03 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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試料の構成要素
+全体 : Cryo-EM structure of archazolid A bound to yeast VO V-ATPase
+超分子 #1: Cryo-EM structure of archazolid A bound to yeast VO V-ATPase
+分子 #1: V-type proton ATPase subunit c'
+分子 #2: V-type proton ATPase subunit c''
+分子 #3: V0 assembly protein 1
+分子 #4: V-type proton ATPase subunit e
+分子 #5: V-type proton ATPase subunit c
+分子 #6: Yeast V-ATPase subunit f
+分子 #7: V-type proton ATPase subunit d
+分子 #8: V-type proton ATPase subunit a, vacuolar isoform
+分子 #9: Archazolid A
-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: 7.4 |
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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: FEI FALCON IV (4k x 4k) 平均電子線量: 42.0 e/Å2 / 詳細: Prototype Falcon 4i camera |
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): 2.5500000000000003 µm 最小 デフォーカス(公称値): 0.37 µm |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |