Standard Conformations of β-Arches in β-Solenoid Proteins

Strand-turn-strand motifs found in β-helical (more generally, β-solenoid) proteins differ fundamentally from those found in globular proteins. The latter are primarily β-hairpins in which the two strands form an antiparallel β-sheet. In the former, the two strands are relatively rotated by ∼90° around the strand axes so that they interact via the side-chains, not via the polypeptide backbones. We call the latter structures, β-arches, and their turns, β-arcs. In β-solenoid proteins, β-arches stack in-register to form β-arcades in which parallel β-sheets are assembled from corresponding strands in successive layers. The number of β-solenoids whose three-dimensional structures have been determined is now large enough to support a detailed analysis and classification of β-arc conformations. Here, we present a systematic account of β-arcs distinguished by the number of residues, their conformations, and their propensity to stack into arcades with other like or unlike arches. The trends to emerge from this analysis have implications for sequence-based detection and structural prediction of other β-solenoid proteins as well as for identification of amyloidogenic sequences and elucidation of amyloid fibril structures.