8.B.7 The Cl- Channel Peptide Inhibitor (GaTx1) Family
A 3.7-kDa peptide toxin, GaTx1, of 34aas, is a potent and reversible inhibitor of CFTR (TC#3.A.1.202.1), acting from the cytoplasmic side of the membrane. GaTx1 is the first peptide toxin identified that inhibits a chloride channel of known molecular identity. It exhibits high specificity, showing no effect on a panel of nine transport proteins, including Cl- and K+ channels and ABC transporters. GaTx1-mediated inhibition of CFTR channel activity is strongly state-dependent; both potency and efficacy are reduced under conditions of elevated [ATP], suggesting that GaTx1 may function as a non-competitive inhibitor of ATP-dependent channel gating.