On the Significance of Alternating Patterns of Polar and Non-polar Residues in Beta-strands

A common assumption about protein sequences in β-strands is that they have alternating patterns of polar and non-polar residues. It is thought that such patterns reflect the interior/exterior geometry of amino acid residue side-chains on a β-sheet. Here we study the prevalence of simple hydrophobicity patterns in parallel and antiparallel β-sheets in proteins of known structure and in the sequences of amyloidogenic proteins. The occurrence of 32 possible pentapeptide binary patterns (polar (P)/non-polar (N)) is computed in 1911 non-homologous protein structures. Despite their tendency to aggregate in experimentally designed proteins, the purely alternating hydrophobic/polar patterns (PNPNP and NPNPN) are most frequent in β-sheets, typically occurring in antiparallel strands. The overall distribution of the pentapeptide binary patterns is significantly different in strands within parallel and antiparallel sheets. In both types of sheets, complementary patterns (where the hydrophobic and polar residues pair with one another) associate preferentially. We do not find alternating patterns to be common in amyloidogenic proteins or in short fragments involved directly in amyloid formation. However, we do note some similarities between patterns present in amyloidogenic sequences and those in parallel strands.