Structures of a Complete Human V-ATPase Reveal Mechanisms of Its Assembly.
Mol Cell
; 80(3): 501-511.e3, 2020 11 05.
Article
en En
| MEDLINE
| ID: mdl-33065002
ABSTRACT
Vesicular- or vacuolar-type adenosine triphosphatases (V-ATPases) are ATP-driven proton pumps comprised of a cytoplasmic V1 complex for ATP hydrolysis and a membrane-embedded Vo complex for proton transfer. They play important roles in acidification of intracellular vesicles, organelles, and the extracellular milieu in eukaryotes. Here, we report cryoelectron microscopy structures of human V-ATPase in three rotational states at up to 2.9-Å resolution. Aided by mass spectrometry, we build all known protein subunits with associated N-linked glycans and identify glycolipids and phospholipids in the Vo complex. We define ATP6AP1 as a structural hub for Vo complex assembly because it connects to multiple Vo subunits and phospholipids in the c-ring. The glycolipids and the glycosylated Vo subunits form a luminal glycan coat critical for V-ATPase folding, localization, and stability. This study identifies mechanisms of V-ATPase assembly and biogenesis that rely on the integrated roles of ATP6AP1, glycans, and lipids.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
ATPasas de Translocación de Protón Vacuolares
Límite:
Humans
Idioma:
En
Año:
2020
Tipo del documento:
Article