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.[13]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.
During the process of acid secretion, the cellular pH increases, triggering the release of the "trigger" loop from the cytoplasmic domain.[14]This allows for the re-arrangement of the TM helices, while the CTD loop is forced out, enabling HCO3- binding. Further conformational changes then turn the AE2 protein into an outward-facing conformation, releasing HCO3- into the extracellular environment and capturing Cl- into the binding pocket. Finally, the AE2 protein returns to its inward-facing conformation and releases Cl- 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 re-balancing pH homeostasis.
^Huang QR, Li Q, Chen YH, Li L, Liu LL, Lei SH, et al. (June 2010). "Involvement of anion exchanger-2 in apoptosis of endothelial cells induced by high glucose through an mPTP-ROS-Caspase-3 dependent pathway".Apoptosis.15(6): 693–704.doi:10.1007/s10495-010-0477-9.PMID20180022.S2CID25917589.
Gehrig H, Müller W, Appelhans H (April 1992). "Complete nucleotide sequence of band 3 related anion transport protein AE2 from human kidney".Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression.1130(3): 326–328.doi:10.1016/0167-4781(92)90446-7.PMID1562608.
Havenga MJ, Bosman GJ, Appelhans H, De Grip WJ (August 1994). "Expression of the anion exchanger (AE) gene family in human brain. Identification of a new AE protein: AE0".Brain Research. Molecular Brain Research.25(1–2): 97–104.doi:10.1016/0169-328X(94)90283-6.PMID7984058.
Medina JF, Acín A, Prieto J (January 1997). "Molecular cloning and characterization of the human AE2 anion exchanger (SLC4A2) gene".Genomics.39(1): 74–85.doi:10.1006/geno.1996.4467.PMID9027488.S2CID223493.
Jöns T, Drenckhahn D (March 1998). "Anion exchanger 2 (AE2) binds to erythrocyte ankyrin and is colocalized with ankyrin along the basolateral plasma membrane of human gastric parietal cells".European Journal of Cell Biology.75(3): 232–236.doi:10.1016/s0171-9335(98)80117-9.PMID9587054.
Mobasheri A, Golding S, Pagakis SN, Corkey K, Pocock AE, Fermor B, et al. (1999). "Expression of cation exchanger NHE and anion exchanger AE isoforms in primary human bone-derived osteoblasts".Cell Biology International.22(7–8): 551–562.doi:10.1006/cbir.1998.0299.PMID10452823.S2CID12201584.
Hyde K, Harrison D, Hollingsworth MA, Harris A (September 1999). "Chloride-bicarbonate exchangers in the human fetal pancreas".Biochemical and Biophysical Research Communications.263(2): 315–321.doi:10.1006/bbrc.1999.1367.PMID10491290.
Medina JF, Lecanda J, Acín A, Ciesielczyk P, Prieto J (January 2000). "Tissue-specific N-terminal isoforms from overlapping alternate promoters of the human AE2 anion exchanger gene".Biochemical and Biophysical Research Communications.267(1): 228–235.doi:10.1006/bbrc.1999.1951.PMID10623603.S2CID26957969.
Vince JW, Reithmeier RA (May 2000). "Identification of the carbonic anhydrase II binding site in the Cl(-)/HCO(3)(-) anion exchanger AE1".Biochemistry.39(18): 5527–5533.doi:10.1021/bi992564p.PMID10820026.
Soleimani M, Greeley T, Petrovic S, Wang Z, Amlal H, Kopp P, Burnham CE (February 2001). "Pendrin: an apical Cl−/OH−/HCO3−exchanger in the kidney cortex ".American Journal of Physiology. Renal Physiology.280(2): F356–F364.doi:10.1152/ajprenal.2001.280.2.f356.PMID11208611.