title: Peptides that form β-sheets on hydrophobic surfaces accelerate surface-induced insulin amyloidal aggregation.
abstract: Interactions between proteins and material or cellular surfaces are able to trigger protein aggregation in vitro and in vivo. The human insulin peptide segment LVEALYL is able to accelerate insulin aggregation in the presence of hydrophobic surfaces. We show that this peptide needs to be previously adsorbed on a hydrophobic surface to induce insulin aggregation. Moreover, the study of different mutant peptides proves that its sequence is less important than the secondary structure of the adsorbed peptide on the surface. Indeed, these pro-aggregative peptides act by providing stable β-sheets to incoming insulin molecules, thereby accelerating insulin adsorption locally and facilitating the conformational changes required for insulin aggregation. Conversely, a peptide known to form α-helices on hydrophobic surfaces delays insulin aggregation.
authors.affiliation: Laboratoire des Matériaux et du Génie Physique, Phelma-Minatec, 3 Parvis Louis Néel CS 50257, F-38016 Grenoble Cedex 1, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Nault
authors.forename: Charlotte
authors.initials: C
authors.lastname: Vendrely
authors.forename: Yves
authors.initials: Y
authors.lastname: Bréchet
authors.forename: Franz
authors.initials: F
authors.lastname: Bruckert
authors.forename: Marianne
authors.initials: M
authors.lastname: Weidenhaupt
mesh_terms: D000327:Adsorption; D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007328:Insulin / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D009154:Mutation; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D055503:Protein Multimerization / Q000187:drug effects*; D017433:Protein Structure, Secondary; D013499:Surface Properties
chemical_list: D000682:Amyloid; D007328:Insulin; D010446:Peptide Fragments