The Supramolecular Chemistry of β-Sheets

Abstract

Interactions among β-sheets occur widely in protein quaternary structure, protein–protein interaction, and protein aggregation and are central in Alzheimer’s and other amyloid-related diseases. This Perspective looks at the structural biology of these important yet under-appreciated interactions from a supramolecular chemist’s point of view. Common themes in the supramolecular interactions of β-sheets are identified and richly illustrated though examples from proteins, amyloids, and chemical model systems. β-Sheets interact through edge-to-edge hydrogen bonding to form extended layers and through face-to-face hydrophobic or van der Waals interactions to form layered sandwich-like structures. Side chains from adjacent layers can fit together through simple hydrophobic contacts or can participate in complementary interdigitation or knob–hole interactions. The layers can be aligned, offset, or rotated. The right-handed twist of β-sheets provides additional opportunities for stabilization of edge-to-edge contacts and rotated layered structures.