An SS1–SS2 β-barrel structure for the voltage-activated potassium channel

Abstract

To examine the feasibility of a β structure for the pore-lining region of the voltage-gated potassium channel, we have characterized a family of 12 antiparallel β-barrels. Each is comprised of four identical pairs of β-strands organized with approximate 4-fold symmetry about a channel axis. The Cand N-termini of the β-strand pairs are assumed to be at the extracellular end of the channel, and each pair is connected by a hairpin turn at the intracellular end of the channel. The models differ in the residues located in the hairpin turn and in the orientation of the two strands of each pair in the barrel, i.e. whether the C-terminus of a pair is clockwise (CW) or counterclockwise (CCW) from the N-terminus when the channel is viewed from outside the cell. Following known structure precedents and potential energy predictions, the barrel is assumed to be right-twisting in all cases. All models have crowded layers of inward-projecting aromatic sidechains near the center of the channel which could regulate channel selectivity. The models with an odd number of amino acids in the hairpin turn have the advantage of predicting that F433 points into the barrel, but the disadvantage that V438 does not. Of these models, two of the models are most consistent with the external tetraethylanunonhim (TEA) block data, and of those, one (T439 CCW 3:5) is most consistent with the internal TEA block data.