The gramicidin A transmembrane channel: a proposed pi(L,D) helix

A lipophilic, left-handed helical structure is proposed for gramicidin A in which the C-O bonds alternately point toward the amino and carboxyl ends; it is a hybrid of the 4.3(14) and 4.4(16) helices. The C-O groups pointing toward the carboxyl end form part of 16-membered hydrogen-bonded rings, whereas the C-O moieties pointing toward the amino end form 14-membered hydrogenbonded rings. The proposed structure is based on conformational analysis combined with requirements for the gramicidin A transmembrane channel. Two helices combine to form the channel. The alternating C-O directions allow hydrogen-bonded dimerization by the unique possibilities of head-to-head and tail-to-tail attachment. The formyl group at the amino end allows for a favorable head-to-head attachment with no loss of structural continuity. Unpublished studies. by M. C. Goodall on the lipid bilayer conductance of deformyl gramicidin A strongly argue for head-to-head attachment. Such hydrogen-bonded association is not possible with previously described helices, as the C-O groups all point in the same direction. In relation to possible pi((L,D)) helices in mammalian systems, it should be noted that glycines would fill the role of D residues. The conformation can undergo ion-induced relaxations, which provide approximate tetrahedral coordination for the ion, with facile shifting of coordinations. The ready exchange of coordinations provides the mechanism for movement of the ion along the channel. Conceivably, such transmembrane channels could have application as models for ion transport across biological membranes-an application which may be as great as, or greater than, that of carriers such as valinomycin and nonactin. Specifically, biogenic amines and drugs containing aromatic groups could control access to the channel by interactions with the two tryptophan residues at the ethanolamine end and with the negative region provided by the three oxygens.