Figure 5: Selectivity of PcTx1 for ASIC1 channels.
From: Structure of the Acid-sensing ion channel 1 in complex with the gating modifier Psalmotoxin 1
Chicken ASIC1 residues of both the hydrophobic patch and the basic cluster that contribute the most to PcTx1 binding are not conserved among different ASICs. (a) The view on the ASIC1 helix 5 shows two subunits of ASIC1 (yellow and blue ribbon) and PcTx1 (transparent surface). The tight van der Waals interaction of Phe351 with the hydrophobic patch of PcTx1 is not retained in ASIC2, ASIC3 and ASIC4 channels that provide Leu, Ala or Ser residues instead. (b) Interactions between Phe174 and Arg27 of the basic cluster are important for PcTx1 binding. The interactions are retained at low pH if Phe174 is exchanged for His, as in human ASIC1 channels. In ASIC2, ASIC3 and ASIC4, Lys, Arg or Asn at position Phe174 introduce a positive charge and abolish binding. (c) Aperture of the Phe351, Phe174 and Gln179 regions in a sequence alignment of ASIC1 channel of various species. Light blue, dark blue and grey depict consensus regions; the rectangle highlights the position of the three ASIC1 residues crucial for selective PcTx1 binding.
