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Calmodulin interacts with amphiphilic peptides composed of all D-amino acids

Nature volume 368, pages 651–653 (1994)Cite this article

Abstract

CALMODULIN binds to amphiphilic, helical peptides of a variety of amino-acid sequences1–8. These peptides are usually positively charged, although there is spectroscopic evidence that at least one neutral peptide binds5. The complex between calmodulin and one of its natural target peptides, the binding site for calmodulin on smooth muscle myosin light-chain kinase (RS20)9, has been investigated by crystallography10 and NMR11–13 which have characterized the interactions between the ligand and the protein. From these data, it appears that the calmodulin-binding surface is ster-ically malleable and van der Waals forces probably dominate the binding. To explore further this apparently permissive binding, we investigated the chiral selectivity of calmodulin using synthesized analogues of melittin and RS20 that consisted of only D-amino acids. Fluorescence and NMR measurements show that D-melittin and D-RS20 both bind avidly to calmodulin, probably in the same general binding site as that for peptides having all i -amino acids. The calmodulin–peptide binding surface is therefore remarkably tolerant sterically. Our results suggest a potentially useful approach to the design of non-hydrolysable or slowly hydrolysable intracellular inhibitors of calmodulin.

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Authors and Affiliations

  1. Department of Pharmacology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota, 55905, USA

    Phyllis J. Fisher, Franklyn G. Prendergast & Salah S. Sedarous

  2. Department of Biochemistry and Molecular Biology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota, 55905, USA

    Daniel J. McCormick & Paul J. Buckley

  3. Department of Biochemistry, School of Chemical Sciences, University of Illinois at Urbana–Champaign, 600 South Mathews Street, Urbana, Illinois, 61801, USA

    Mark R. Ehrhardt, Jeffrey L. Urbauer & A. Joshua Wand

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  1. Phyllis J. Fisher
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  2. Franklyn G. Prendergast
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Fisher, P., Prendergast, F., Ehrhardt, M. et al. Calmodulin interacts with amphiphilic peptides composed of all D-amino acids. Nature 368, 651–653 (1994). https://doi.org/10.1038/368651a0

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