Abstract
A series of helical structures for gramicidin A, with alternating L and D residues, are characterized as to number of residues per turn, atoms in hydrogenbonded rings, and dihedral angles. Because of alternating peptide C-O directions, these helices are capable of forming head-to-head hydrogen-bonded dimers with the capacity of functioning as transmembrane channels. The dimers are characterized as to channel length, pore size, and expected ion selectivity.
In a test of the proposed head-to-head association for channel formation, the malonyl dimer [N,N′-(dideformyl gramicidin A)-malonamide] was synthesized. The chemical and conformational integrity of the product was verified by nuclear magnetic resonance; in lipid bilayer studies, the dimer was found to be a potent mediator of ion conductance with the predicted concentration dependence.
Thus, the results on malonyl gramicidin A prove head-to-head association in formation of the transmembrane channel, and the results are consistent with the specific geometrical configuration involved in head-to-head dimerization of π(L,D) helices. At this stage, the action of gramicidin A on membranes with lipid-layer thicknesses of 30 Å or less can best be understood in terms of the π(L,D) helix with 6.3 residues per turn.
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Selected References
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- Donohue J. Hydrogen Bonded Helical Configurations of the Polypeptide Chain. Proc Natl Acad Sci U S A. 1953 Jun;39(6):470–478. doi: 10.1073/pnas.39.6.470. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goodall M. C. Structural effects in the action of antibiotics on the ion permeability of lipid bilayers. 3. Gramicidins "A" and "S", and lipid specificity. Biochim Biophys Acta. 1970 Dec 1;219(2):471–478. doi: 10.1016/0005-2736(70)90225-7. [DOI] [PubMed] [Google Scholar]
- Goodall M. C. Structural effects in the action of antibiotics on the ion permeability of lipid bilayers. I. Tyrocidine B. Biochim Biophys Acta. 1970 Mar 17;203(1):28–33. doi: 10.1016/0005-2736(70)90032-5. [DOI] [PubMed] [Google Scholar]
- Hladky S. B., Haydon D. A. Discreteness of conductance change in bimolecular lipid membranes in the presence of certain antibiotics. Nature. 1970 Jan 31;225(5231):451–453. doi: 10.1038/225451a0. [DOI] [PubMed] [Google Scholar]
- Ooi T., Scott R. A., Vanderkooi G., Scheraga H. A. Conformation of analysis of macromolecules. IV. Helical structures of poly-L-alanine, poly-L-valine, poly-beta-methyl-L-aspartate, poly-gamma-methyl-L-glutamate, and poly-L-tyrosine. J Chem Phys. 1967 Jun 1;46(11):4410–4426. doi: 10.1063/1.1840561. [DOI] [PubMed] [Google Scholar]
- PAULING L., COREY R. B. Atomic coordinates and structure factors for two helical configurations of polypeptide chains. Proc Natl Acad Sci U S A. 1951 May;37(5):235–240. doi: 10.1073/pnas.37.5.235. [DOI] [PMC free article] [PubMed] [Google Scholar]
- PAULING L., COREY R. B., BRANSON H. R. The structure of proteins; two hydrogen-bonded helical configurations of the polypeptide chain. Proc Natl Acad Sci U S A. 1951 Apr;37(4):205–211. doi: 10.1073/pnas.37.4.205. [DOI] [PMC free article] [PubMed] [Google Scholar]
- RAMACHANDRAN G. N., RAMAKRISHNAN C., SASISEKHARAN V. Stereochemistry of polypeptide chain configurations. J Mol Biol. 1963 Jul;7:95–99. doi: 10.1016/s0022-2836(63)80023-6. [DOI] [PubMed] [Google Scholar]
- SARGES R., WITKOP B. GRAMICIDIN A. V. THE STRUCTURE OF VALINE- AND ISOLEUCINE-GRAMICIDIN A. J Am Chem Soc. 1965 May 5;87:2011–2020. doi: 10.1021/ja01087a027. [DOI] [PubMed] [Google Scholar]
- Urry D. W. The gramicidin A transmembrane channel: a proposed pi(L,D) helix. Proc Natl Acad Sci U S A. 1971 Mar;68(3):672–676. doi: 10.1073/pnas.68.3.672. [DOI] [PMC free article] [PubMed] [Google Scholar]