Detecting Structural Similarity between BK Binding Domains on Iberiotoxin and ASIC1 at Different pH

Previous studies have shown that acid sensing ion channels (ASICs) inhibit calcium‐ and voltage‐activated potassium channels (BK) at physiological pH, and the inhibition is removed at acidic pH (Petroff et al. PNAS 2008; Petroff et al. BBRC 2012). The overlay capabilities of ChemBio3D Ultra 2010 (CambridgeSoft, Cambridge, MA) were used to detect structural similarities between putative BK‐binding domain in ASIC (R 191 G 193 K 194 ) and known iberiotoxin (IbTx) domain critical for BK‐binding (R 25 G 26 K 27 ). We compared the structure of (R 191 G 193 K 194 ) domain of ASIC1 at low pH (PDP ID: 2QTS) to the structure of IbTx (R 25 G 26 K 27 ) domain obtained from Swiss‐Model Repository. We also overlaid the structure of (R 191 G 193 K 194 ) domain of ASIC1 at pH of 7.5 (PDB ID: 3S3W ) against IbTx binding domain (R 25 G 26 K 27 ). Our results show that at pH 7.5, ASIC1's putative BK‐binding domain (R 191 G 193 K 194 ) is structurally more similar to the IbTx BK‐binding domain (R 25 G 26 K 27 ) than at low pH. These in silico findings support the previous experimental studies and indicate that the structure of ASIC1 at neutral pH could favor interaction with BK, while at low pH, the conformational changes in ASIC1 make it less likely. This work is supported by the NIH NS070260 grant to EP. Overlaid R 191 G 193 K 194 domain of ASIC1 at neutral pH against IbTx's BK‐binding domain (R 25 G 26 K 27 ). The distance between the central carbon atoms of each of the residues is shown.Residues Distance (Å) ASIC1 ‐ IbTxR 191 ‐ R 25 1.0G 193 ‐ G 26 0.9K 194 ‐ K 27 0.4Overlaid R 191 G 193 K 194 domain of ASIC at low pH against IbTx's BK‐binding domain (R 25 G 26 K 27 ). The distance between the central carbon atoms of each of the residues is shown.Residues Distance (Å) ASIC1 ‐ IbTxR 191 ‐ R 25 2.5G 193 ‐ G 26 2.5K 194 ‐ K 27 2.0