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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-25779 | |||||||||
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Title | Cryo-EM structure of bafilomycin A1 bound to yeast VO V-ATPase | |||||||||
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Function / homology | ![]() cell wall mannoprotein biosynthetic process / ATPase-coupled ion transmembrane transporter activity / cellular response to alkaline pH / P-type proton-exporting transporter activity / 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 / cellular response to alkaline pH / P-type proton-exporting transporter activity / Insulin receptor recycling / Transferrin endocytosis and recycling / polyphosphate metabolic process / ROS and RNS production in phagocytes / Amino acids regulate mTORC1 / Golgi lumen acidification / plasma membrane proton-transporting V-type ATPase complex / vacuolar proton-transporting V-type ATPase, V0 domain / endosomal lumen acidification / vacuolar transport / proton-transporting V-type ATPase complex / vacuole organization / protein targeting to vacuole / vacuolar proton-transporting V-type ATPase complex / fungal-type vacuole / vacuolar acidification / cellular hyperosmotic response / fungal-type vacuole membrane / phosphatidylinositol-3,5-bisphosphate binding / proton transmembrane transporter activity / intracellular copper ion homeostasis / RNA endonuclease activity / Neutrophil degranulation / proton transmembrane transport / proton-transporting ATPase activity, rotational mechanism / cell periphery / transmembrane transport / ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() ![]() | |||||||||
Method | ![]() ![]() | |||||||||
![]() | Keon KA / Rubinstein JL / Benlekbir S / Kirsch SH / Muller R | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Cryo-EM of the Yeast V Complex Reveals Distinct Binding Sites for Macrolide V-ATPase Inhibitors. Authors: Kristine A Keon / Samir Benlekbir / Susanne H Kirsch / Rolf Müller / John L Rubinstein / ![]() ![]() Abstract: 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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Structure visualization
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 59.7 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 17 KB 17 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 9.5 KB | Display | ![]() |
Images | ![]() | 80.1 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7taoMC ![]() 7tapC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Voxel size | X=Y=Z: 1.20703 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
+Entire : Cryo-EM structure of bafilomycin A1 bound to yeast VO V-ATPase
+Supramolecule #1: Cryo-EM structure of bafilomycin A1 bound to yeast VO V-ATPase
+Macromolecule #1: V-type proton ATPase subunit c'
+Macromolecule #2: V-type proton ATPase subunit c''
+Macromolecule #3: V0 assembly protein 1
+Macromolecule #4: V-type proton ATPase subunit e
+Macromolecule #5: V-type proton ATPase subunit c
+Macromolecule #6: Yeast V-ATPase subunit f
+Macromolecule #7: V-type proton ATPase subunit d
+Macromolecule #8: V-type proton ATPase subunit a, vacuolar isoform
+Macromolecule #9: (5R)-2,4-dideoxy-1-C-{(2S,3R,4S)-3-hydroxy-4-[(2R,3S,4E,6E,9R,10S...
-Experimental details
-Structure determination
Method | ![]() |
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Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 39.0 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |