The air-water interface stabilizes α-helical conformations of the insulin B-chain

Abstract

Adsorption of proteins onto liquid interfaces, such as the air-water interface, often leads to changes in the protein conformation. This can lead to changes in protein assembly behaviour, with aggregation and fibrillation often enhanced. To understand the relationship between protein conformation and aggregation, knowledge of protein structure at interfaces, on the single molecular level, is necessary. Using molecular dynamics simulations the effect of the air-water interface on conformation of the insulin B-chain is investigated. At the air-water interface the protein adopts an α-helical conformation, whereas in bulk solution it adopts disordered structures. The α-helical conformation is templated by the partitioning of hydrophobic side chains into the air, leading to the formation of an amphipathic helix. This structure presents a hydrophobic face which may lead to further aggregation, which helps explain the enhancement of insulin fibrillation at interfaces. This knowledge of the molecular conformation gives new insight into the contribution of protein structural change on the interfacial aggregation of proteins.

Effect of the Air-Water Interface on the Conformation of Amyloid Beta

“…The simulated systems consist of a single protein molecule (Aβ (16)(17)(18)(19)(20)(21)(22), Aβ (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35), or Aβ(10-40) fragment) in water. For Aβ(10-40) and Aβ (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)the initial peptide structures were taken from experimental NMR structures (1IYT 27 and 1QYT 28 ), with the first nine and last two residues removed for Aβ(10-40).…”

“…For Aβ(10-40) and Aβ (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)the initial peptide structures were taken from experimental NMR structures (1IYT 27 and 1QYT 28 ), with the first nine and last two residues removed for Aβ(10-40). The initial structure for Aβ (16)(17)(18)(19)(20)(21)(22) was taken to be a linear chain constructed using Avogadro. Protonation states of the termini and for polarisable residues were set appropriate for pH=7.…”

“…for Aβ(10-40) Aβ (16)(17)(18)(19)(20)(21)(22) and Aβ (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) respectively, with the box tripled in the z-direction to give a vacuum layer on each side of the slab. For the bulk simulations the protein was was placed in a cubic water box with side length 70Å, 40Å, and 50Å for Aβ(10-40) Aβ (16)(17)(18)(19)(20)(21)(22) and Aβ (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) respectively.…”

“…To aid understanding of the fibrillation process it is common to investigate fragments of larger proteins. For Aβ commonly these include the Aβ(10-40) fragment, which lacks the Nterminal region which remains disordered following fibril formation 23 , Aβ (16)(17)(18)(19)(20)(21)(22) fragment, which contains the central hydrophobic core of the protein, and Aβ (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) fragment, which is the smallest fragment to show the same neurotoxic effects of the full protein 24 . While it may be expected that these fragments should mimic that of the full protein, in some cases these can show significantly different behaviour.…”

“…In this paper the behaviour of three fragments of Aβ, Aβ (16)(17)(18)(19)(20)(21)(22), Aβ (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35), and Aβ(10-40), is investigated at the air-water interface (AWI), a model hydrophobic-hydrophilic interface. Comparison with the structures found in bulk solution shows that, in common with studies of other IDPs, the AWI induces the formation of ordered structures.…”