The disruption of the third extracellular loop of the red cell anion exchanger AE1 does not affect electroneutral Cl^-/HCO₃ ^- exchange activity

The red cell anion exchanger (band 3; AE1) is a multispanning membrane protein that traverses the bilayer up to 14 times and mediates the stilbene-disulfonate-sensitive, electroneutral exchange of chloride and bicarbonate. Previous studies showed that the integrity of the third extracellular loop (EC3) of the protein was not essential for stilbene-disulfonate-sensitive chloride uptake. Here we demonstrate that the chloride uptake mediated by assemblies separated at EC3 represents the physiological electroneutral Cl^-/HCO₃^- activity associated with intact AE1 protein. This provides further evidence that the 1:5 and 6:14 regions of the protein form discrete folding domains and confirms that the third extracellular loop does not play a pivotal role in AE1 transport function.