6WM4

Human V-ATPase in state 3 with SidK and ADP

Summary for 6WM4

• Entry DOI: 10.2210/pdb6wm4/pdb
• EMDB information: 21849
• Descriptor: V-type proton ATPase 116 kDa subunit a isoform 1, V-type proton ATPase subunit D, V-type proton ATPase subunit F, ... (19 entities in total)
• Functional Keywords: pump, membrane protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 35
• Total formula weight: 1251003.49

Authors

Wang, L.,Wu, H.,Fu, T.M. (deposition date: 2020-04-20, release date: 2020-11-11, Last modification date: 2024-11-06)

Primary citation

Wang, L.,Wu, D.,Robinson, C.V.,Wu, H.,Fu, T.M.
Structures of a Complete Human V-ATPase Reveal Mechanisms of Its Assembly.
Mol.Cell, 80:501-, 2020

PubMed Abstract: Vesicular- or vacuolar-type adenosine triphosphatases (V-ATPases) are ATP-driven proton pumps comprised of a cytoplasmic V complex for ATP hydrolysis and a membrane-embedded V 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 V complex. We define ATP6AP1 as a structural hub for V complex assembly because it connects to multiple V subunits and phospholipids in the c-ring. The glycolipids and the glycosylated V 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.

PubMed: 33065002
DOI: 10.1016/j.molcel.2020.09.029

Experimental method

ELECTRON MICROSCOPY (3.6 Å)