A Reevaluation of the Structure in the Pore Region of Voltage-Activated Cation Channels

Members of the Voltage-Sensitive Cation Channel (VSCC) superfamily from highly selective voltage-gated pores in excitable membranes. These pores are thought to be formed from the extrucellulur loops thut interconnect transmembrane segments 5 und 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 β-turn in the S5-S6 loop of each of 80 domains from the VSCC superfumily (26 different channel isoforms) were identified and located on the basis of their significant local maxima for {beta}-turn propensity (Pbend). Significant β-turns were identified in all 80 sequences, but they are shtifted, and lie in the region currently defined as the SS2 β-strand. This location of the β-turn is incompatible with an antiparallel β-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.