Design of single-layer β-sheets without a hydrophobic core.

摘要: The hydrophobic effect is the main thermodynamic driving force in folding of water-soluble proteins1,2. Exclusion nonpolar moieties from aqueous solvent results formation a core protein, which has been generally considered essential for specifying and stabilizing folded structures proteins1,2,3,4,5,6. Outer surface protein A (OspA) Borrelia burgdorferi contains three-stranded β-sheet segment connects two globular domains7. Although this single-layer exposed to on both faces thus does not contain core, high conformational stability8. Here we report engineering OspA variants that larger β-sheets (comprising five seven β-strands) by duplicating β-hairpin unit within β-sheet. Nuclear magnetic resonance small-angle X-ray scattering analyses reveal these extended are formed as designed, amide hydrogen–deuterium exchange chemical denaturation show they stable. Thus, interactions those between adjacent units, do involve sufficient specify stabilize structure. Our provide an expanded view folding, misfolding design.