title: The role of the disulfide bond in the interaction of islet amyloid polypeptide with membranes.
abstract: Human islet amyloid polypeptide (hIAPP) forms amyloid fibrils in pancreatic islets of patients with type 2 diabetes mellitus. It has been suggested that the N-terminal part, which contains a conserved intramolecular disulfide bond between residues 2 and 7, interacts with membranes, ultimately leading to membrane damage and beta-cell death. Here, we used variants of the hIAPP(1-19) fragment and model membranes of phosphatidylcholine and phosphatidylserine (7:3, molar ratio) to examine the role of this disulfide in membrane interactions. We found that the disulfide bond has a minor effect on membrane insertion properties and peptide conformational behavior, as studied by monolayer techniques, (2)H NMR, ThT-fluorescence, membrane leakage, and CD spectroscopy. The results suggest that the disulfide bond does not play a significant role in hIAPP-membrane interactions. Hence, the fact that this bond is conserved is most likely related exclusively to the biological activity of IAPP as a hormone.
authors.forename: Lucie
authors.initials: L
authors.lastname: Khemtémourian
authors.forename: Maarten F M
authors.initials: MF
authors.lastname: Engel
authors.forename: John A W
authors.initials: JA
authors.lastname: Kruijtzer
authors.forename: Jo W M
authors.initials: JW
authors.lastname: Höppener
authors.forename: Rob M J
authors.initials: RM
authors.lastname: Liskamp
authors.forename: J Antoinette
authors.initials: JA
authors.lastname: Killian
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry*; D002462:Cell Membrane / Q000378:metabolism*; D004220:Disulfides; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology* / Q000378:metabolism*; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary
chemical_list: D000682:Amyloid; D004220:Disulfides; D010446:Peptide Fragments; D010713:Phosphatidylcholines; D010718:Phosphatidylserines; C050294:1-palmitoyl-2-oleoylglycero-3-phosphoserine; C028694:1-palmitoyl-2-oleoylphosphatidylcholine