Effects of mutagenesis of W343 in human annexin A6 isoform 1 on its interaction with GTP : Nucleotide-induced oligomer formation and ion channel activity

Accumulated experimental evidence suggests that annexin A6 (AnxA6) is involved in ion transport in various tissues. Such a biological function is related either to the modulation of ion transport systems by AnxA6 or to the ion channel activity of the protein. While AnxA6 channel activity at low pH seems to be associated with a large conformational transition in the protein, the mechanism of GTP-induced ion channel formation remains obscure. This activity is not accompanied by changes in protein structure. The existence of a domain binding the phosphate groups of GTP in AnxA6 [Bandorowicz-Pikula, J., Kirilenko, A., van Deursen, R., Golczak, M., Kuhnel, M., Lancelin, J. M., Pikula, S., and Buchet, R. (2003) Biochemistry 42, 9137−9146] may provide some clues about the molecular mechanisms of GTP-induced ion channel formation. In addition, we observed that one of the AnxA6 tryptophan residues, W192 or W343, may be involved in GTP binding. Therefore, we created several site-directed mutants of AnxA6 in which s...