A REEVALUATION OF THE STRUCTURE IN THE PORE REGION OF VOLTAGE-ACTIVATED CATION CHANNELS

Members of the Voltage-Sensitive Cation Channel (VSCC) superfamily form highly selective voltage-gated pores in excitable membranes. These pores are thought to be formed formed the extracellular loops that interconnect transmembrane segments 5 and 6 in each of the four domains that constitute the channel. Each of these loops is currently modeled as consisting of two short segments, SS1 and SS2, that are linked by a hairpin turn to form an antiparallel structure. In this study, the hypothesized beta- turn in the S5-S6 loop of each of 80 domains from the VSCC superfamily (26 different channel isoforms) were identified and located on the basis of their significant local maxima for beta-turn propensity (P-bend). Significant beta-turns were identified in all 80 sequences, but they are shifted, and lie in the region currently defined as the SS2 beta-strand. This location of the beta-turn is incompatible with an antiparallel beta-sheet structure of the pore. The region identified here as forming the turn corresponds to the ion selective determinants in the pore, implying that the turn imparts some of the ionic selectivity of each channel.