A molecular theory of ion-conductng channels: a field-dependent transition between conducting and nonconducting conformations.

Abstract

Structural and conformational requirements for an electric field-dependent transition between conducting and nonconducting macromolecular systems are: two kinetically interconvertible and energetically similar conformations, one conducting and the other nonconducting, which have axes spanning the lipid layer of biological membranes, but which have different net dipole moments along those axes. Two examples are described. A previously defined helix, the pi(6)LD-helix now termed the beta(6) (3,3)-helix, is proposed as the conducting species, and the linear peptide correlate of the cyclic hexapeptide conformation containing two beta-turns and an inversion element of symmetry is proposed as a nonconducting species. The latter is termed an anti-beta(6) (2)-spiral and contains little or no net dipole moment per turn, whereas the beta(6) (3,3)-helix contains a net dipole moment along the helix axis of about 0.5 Debye per dipeptide unit. A related conducting and nonconducting pair with large net dipole moments of opposite sign, termed syn-beta(6) (2)-spiral and beta(6) (2,4)-helix, are also described. The spiral conformations are stabilized in a lipid layer by intermolecular hydrogen bonds, leading to a linear association of transmembrane structures. A conformational transition in one member of the array could lead to destabilization of an adjacent member of the array. The conformational analysis uses a concept of cyclic conformations with linear conformational correlates. The anti-beta(6) (2)-spiral and beta(6) (3,3)-helix are derivable from the conformations of the cyclic structure [unk], whereas the syn-beta(2)-spiral and beta(6) (2,4)-helix may be derived from the cyclic structure [unk].The conformational analysis leads to the expectation that N-formyl-(L-Ala-L-Ala-Gly)(n) would form conducting channels.