Structural and functional analysis of extracellular loop 4 of the Nhe1 isoform of the Na+/H+ exchanger

► We characterized extracellular loop 4 of the Na+/H+ exchanger. ► Residues F277, F280, N282 and E284 of EL4 were reactive with external MTSET. ► EL4 was unstructured and it may serve as a flexible linkage between transmembrane segments. ► EL4 extends from transmembrane segment VII to make up part of the cation channel.