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Gramicidin channel controversy — revisited

Nature Structural Biology volume 6, pages 610–611 (1999)Cite this article

We are writing in response to an editorial published in Nature Structural Biology1, which highlighted events at an American Crystallographic Association meeting. In particular, the editorial highlighted a presentation by William Duax of two "new" intertwined double-stranded (DS) gramicidin A structures, one crystallized from a CsCl saturated methanol solution and one from glacial acetic acid. They were promoted as the channel structure in membranes. Furthermore, in the editorial it was stated that the "new" structures "correlate well with previous data on the biochemistry and biophysics of the channel in the membrane, unlike the ... [single-stranded (SS)] conformations". We point out that while the "new" structures add to the cadre of DS X-ray structures of this polymorphic molecule, these structures were previously characterized by solution NMR in a similar solvent system2. Here we present our view that the "new" structure does not correlate well with the experimental data obtained from a lipid environment, which uniquely defines the SS structure. We also describe why the SS and not the DS structure of gramicidin A dominates in lipid bilayers.

While gramicidin A forms a variety of double-helical structures in organic solvents, these structures are not thermodynamically stable in lipid bilayers14,15. The primary reason for this is that the antiparallel DS structures would bury indoles in the low dielectric environment of the membrane. The SS structures characterized in a lipid environment have the indoles in the more hydrophilic interfacial region. Through experiments that replace the Trp with Phe residues it has been clearly shown that the indoles generate the driving force that destabilizes the DS structure while stabilizing the SS structure16,17. This heterogeneous nature of the membrane environment is not modeled by isotropic organic solvents18 and there is no evidence that the DS structures are the membrane channel form.

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Figure 1: a, Channel SS conformation of gramicidin A (PDB code 1MAG) determined by solid state NMR in uniformly aligned lamellar phase lipid bilayers.

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Authors and Affiliations

  1. Department of Chemistry, Institute of Molecular Biophysics and National High Magnetic Field Laboratory, Florida State University, Tallahassee, 32310, Florida, USA

    T.A. Cross

  2. Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117871, Russia

    A. Arseniev

  3. Cooperative Research Centre for Molecular Engineering & Technology, Chatswood, 2067, NSW, Australia

    B.A. Cornell

  4. Department of Physics, University of Guelph, N1G 2W1, Ontario, Canada

    J.H. Davis

  5. Department of Biochemistry of Membranes, University of Utrecht, Utrecht, 3584 CH, The Netherlands

    J.A. Killian

  6. Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, 72701, Arizona, USA

    R.E. Koeppe II

  7. Section of Biochemistry, Molecular and Cell Biology, Cornell University, Ithaca, 14853, New York, USA

    L.K. Nicholson

  8. School of Chemistry, University of Melbourne, Victoria, 3052, Australia

    F. Separovic

  9. Department of Crystallography, University of London, London, WC1E 7HX, England

    B.A. Wallace

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Cross, T., Arseniev, A., Cornell, B. et al. Gramicidin channel controversy — revisited. Nat Struct Mol Biol 6, 610–611 (1999). https://doi.org/10.1038/10650

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