Is CFTR an Archetypal “Primitive Pore”?
Smith et al51 speculated that the lyotropic, bias-based selectivity of CFTR suggested that it was a “primitive” structure that, for one reason or another, had not evolved a mechanism for the highly selective recognition of Cl- ions. Selectivity for Cl- is indeed somewhat optimized in CFTR, but in a roundabout way. Smaller anions, like F-, have difficulty entering the pore due to their relatively high energy of hydration. Large molecules like SCN- actually appear to enter the pore more readily than Cl- (due to their lower ΔGhyd) but are retarded in their passage by a deeper energy well in the conduction path. The end result is a channel that is, in fact, only moderately selective, permitting ions like Br- and NO3- to transit with ease, but which seems nevertheless to serve its function admirably. Perhaps it is the relatively low abundance of these competing ions that reduced the pressure for the evolution of a more selective structure.
