title: Beta-sheet models for the ordered filamentous structure formed by a peptide that enhances the action of insulin.
abstract: Certain peptides with sequences related to part of the major histocompatibility complex class I antigen enhance the action of insulin. These peptides also aggregate into fibrous structures that seem to be related to their biological activity. In the current study, the 17-residue peptide with amino acid sequence Gly-Asn-Glu-Gln-Ser-Phe-Arg-Val-Asp-Leu-Arg-Thr-Leu-Leu-Arg-Tyr-Ala is used as a representative example of these bioactive molecules. As seen by electron microscopy, the peptide associates into gently twisted ribbons, 50 A thick, in which the amount of twist decreases as the ribbons become wider. X-ray diffraction analysis suggests 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 predominantly polar while the opposite side is nonpolar. This allows the beta-sheets to form multilayers with alternating hydrophobic and hydrophilic interfaces. The length of the extended peptide (approximately 54 A) determines the thickness of the ribbon and the tendency of individual 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-side" fashion rather than forming stacked layers. Comparable inactive peptides such as Gly-Asn-Glu-Gln-Ser-Ala-Arg-Val-Asp-Leu-Arg-Thr-Leu-Leu-Arg-Tyr-Tyr (changed amino acids underlined) do not form ordered filamentous structures.
authors.affiliation: Institute of Molecular Biology, Howard Hughes Medical Institute and Department of Physics, University of Oregon, Eugene, Oregon, 97403, USA.
authors.forename: L
authors.initials: L
authors.lastname: Weaver
authors.forename: J
authors.initials: J
authors.lastname: Stagsted
authors.forename: O
authors.initials: O
authors.lastname: Behnke
authors.forename: B W
authors.initials: BW
authors.lastname: Matthews
authors.forename: L
authors.initials: L
authors.lastname: Olsson
mesh_terms: D000595:Amino Acid Sequence; D004357:Drug Synergism; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D008854:Microscopy, Electron; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D017433:Protein Structure, Secondary; D014961:X-Ray Diffraction
chemical_list: D007328:Insulin; D010455:Peptides