The role of the disulfide bond in the interaction of islet amyloid polypeptide with membranes.

Lucie Khemtémourian (1, 2) , Maarten F M Engel , John a W Kruijtzer , Jo W M Höppener , Rob M J Liskamp , J Antoinette Killian

1 UPMC - Université Pierre et Marie Curie - Paris 6
2 CBMN - Chimie et Biologie des Membranes et des Nanoobjets

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.

Domaines: Chimie organique

Lucie Khemtémourian, Maarten F M Engel, John a W Kruijtzer, Jo W M Höppener, Rob M J Liskamp, et al.. The role of the disulfide bond in the interaction of islet amyloid polypeptide with membranes.. Biophysics of structure and mechanism, 2010, 39 ((9)), pp.1359-64. ⟨10.1007/s00249-009-0572-4⟩. ⟨hal-00614578⟩