Interchain hydrogen-bonding interactions may facilitate translocation of K+ ions across the potassium channel selectivity filter, as suggested by synthetic modeling chemistry

A 4-fold symmetric arrangement of TVGYG polypeptides forms the selectivity filter of the K+ channel from Streptomyces lividans (KcsA). We report the s ynthesis and properties of synthetic models for the filter, p-tert-butyl-ca lix[4]arene-(OCH2CO-XOBz)(4) (X = V, VG, VGY), 1-3. The first cation (Na+, K+) binds to the four -{OCH2CO}- units, a region devised to mimic the metal -binding site formed by the four T residues in KcsA. NMR studies reveal tha t cations and valine amide protons compete for the carbonyl oxygen atoms, c onverting N-H-val. . .O=C hydrogen bonds to M+. . .O=C bonds (M+ = Na+ or K +). The strength of these interchain N-H-val. . .O=C hydrogen bonds varies in the order 3 > 2 > 1. We propose that such interchain H-bonding may desta bilize metal binding in the selectivity filter and thus help create the low energy barrier needed for rapid cation translocation.