Human V-ATPase a-subunit isoforms bind specifically to distinct phosphoinositide phospholipids.

Area of Science:

• Cell Biology
• Biochemistry
• Molecular Biology

Background:

• Vacuolar-type proton ATPases (V-ATPases) are crucial for maintaining organelle pH.
• The V-ATPase a-subunit's N-terminal domain (aNT) influences enzyme regulation and localization.
• Organelle membranes contain specific phosphatidylinositol phosphate (PIP) lipids that are vital for pH homeostasis.

Conclusions:

• Human V-ATPase aNT domains exhibit distinct PIP lipid binding specificities, correlating with their respective organelle localizations.
• PIP lipid binding likely stabilizes and activates V-ATPases in a manner specific to their organelle environment.
• The distal loops of aNT domains are key determinants of PIP lipid specificity, providing a mechanism for organelle-specific V-ATPase regulation.