Stabilization of the α2 Isoform of Na,K-ATPase by Mutations in a Phospholipid Binding Pocket

Background: The alpha 2 isoform of Na, K-ATPase is unstable compared with alpha 1 and alpha 3. Results: Mutations in TM8-10 strongly stabilize alpha 2. A novel phospholipid antagonist selectively inactivates alpha 2, and mutations in TM8-10 protect against inactivation. Conclusion: A phosphatidylserine binding pocket within TM8-10 has been identified. Significance: Mechanistic insights into alpha 2 instability and a possible physiological role have been obtained.