The geometry of alpha-sheet: implications for its possible function as amyloid precursor in proteins

Hayward, S. and Milner-White, E.J. (2008) The geometry of alpha-sheet: implications for its possible function as amyloid precursor in proteins. Proteins: Structure Function and Bioinformatics, 71(1), pp. 415-425. (doi: 10.1002/prot.21717)

Abstract

α-sheet has been proposed as the main constituent of the prefibrillar intermediate during amyloid formation. Here the helical parameters of the α-sheet strand are calculated from average main-chain dihedral angles reported from molecular dynamics simulations. It is an almost linear polypeptide that forms a right-handed helix of about 100 Å diameter, with 100 residues and a rise of 30 Å per turn. The strands are curved but untwisted, which implies that neighboring strands need not coil to make interstrand hydrogen bonds. This suggests that compared to β-sheets in native folded proteins, α-sheets can be larger and stack more easily to create extensive 3D blocks. It is shown that α-sheet is related to a category of structures termed "mirror" structures. Mirror structures have repetitive pairs of main-chain dihedral angles at residues i and i+1 that satisfy the condition Φ_i+1 =-Ψ_i, Ψ_i+1 = -Φ_i. They are uniquely identified by the two orientations of their peptide planes, specified by Φ_i and Ψ_i. Their side chains point alternately in opposite directions. Interestingly, their conformations are insensitive to Φ_i and Ψ_i in that the pseudo dihedral angle formed by four consecutive C-α atoms is always close to 180°. There are two types: "β-mirror" and "α-mirror" structure, β-mirror structures relate to β-sheet by small peptide plane rotations, of less than 90°, while α-mirror structures are close to α-sheet and relate to β-sheet by ∼180° peptide plane flips. Most mirror structures, and in particular the α-mirror, form wide helices with diameters 50-70Å. Their gentle curvature, and therefore that of the α-sheet, arises from the orientation of successive peptide units causing the difference in the bond angles at the C and N atoms of the peptide unit to gradually change the direction of the chain.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Milner-White, Professor E
• Authors: Hayward, S., and Milner-White, E.J.
• Subjects: Q Science > QH Natural history > QH345 Biochemistry
• College/School: College of Medical Veterinary and Life Sciences
• Journal Name: Proteins: Structure Function and Bioinformatics
• ISSN: 0887-3585
• Published Online: 23 October 2007