BETA-SHEET MODELS FOR THE ORDERED FILAMENTOUS STRUCTURE FORMED BY A PEPTIDE THAT ENHANCES THE ACTION OF INSULIN

Certain peptides with sequences related to part of the major histocomp atibility complex class I antigen enhance the action of insulin, These peptides also aggregate into fibrous structures that seem to be relat ed to their biological activity, In the current study, the 17-residue peptide with amino acid sequence er-Phe-Arg-Val-Asp-Leu-Arg-Thr-Leu-Le u-Arg-Tyr-Ala is used as a representative example of these bioactive m olecules, As seen by electron microscopy, the peptide associates into gently twisted ribbons, 50 Angstrom thick, in which the amount of twis t decreases as the ribbons become wider, X-ray diffraction analysis su ggests that the peptides are arranged as in an antiparallel beta-sheet extending essentially endlessly along the fiber axis, The amino acid sequence of the peptide is such that one side of the beta-sheet is pre dominantly polar while the opposite side is nonpolar, This allows the beta-sheets to form multilayers with alternating hydrophobic and hydro philic interfaces, The Length of the extended peptide (similar to 54 A ngstrom) determines the thickness of the ribbon and the tendency of in dividual beta-sheets to twist accounts for the twisting of the ribbons , An alternative model is also discussed, again based on antiparallel beta-sheets, but with adjacent sheets interdigitated in a ''side-by-si de'' fashion rather than forming stacked layers, Comparable inactive p eptides such as er-Ala-Arg-Val-Asp-Leu-Arg-Thr-Leu-Leu-Arg-Tyr-Tyr (ch anged amino acids underlined) do not form ordered filamentous structur es. (C) 1996 Academic Press