Anion exchange protein 2

The cryo electron microscopic studies revealed that human AE2 protein forms a homodimer and stays in resting state of inward-facing conformation at physiological pH. A loop between transmembrane (TM) helices 10 and 11 extends from TM domain into its cytoplamic domain, forming a "trigger" locking the TM helices in the resting state. In addition, the C-terminal loop (CTD loop) inserts into the anion binding pocket to further block its activities. == Mechanism of ion exchange ==

During the process of acid secretion, the cellular pH increases, triggering the release of the "trigger" loop from the cytoplasmic domain. This allows for the re-arrangement of the TM helices, while the CTD loop is forced out, enabling binding. Further conformational changes then turn the AE2 protein into an outward-facing conformation, releasing into the extracellular environment and capturing into the binding pocket. Finally, the AE2 protein returns to its inward-facing conformation and releases into the cytosol. This working cycle of the AE2 protein replaces a weak acid anion with a strong acid anion, thereby lowering the cellular pH and rebalancing pH homeostasis. == See also ==