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Keywords:

  • β-arch;
  • Greek key β-barrel;
  • Greek key connection;
  • protein folding;
  • protein structure;
  • side-chain hydrogen bonding;
  • tyrosine corner

Abstract

The Tyr corner is a conformation in which a tyrosine (residue “Y”) near the beginning or end of an antiparallel β-strand makes an H bond from its side-chain OH group to the backbone NH and/or CO of residue Y – 3, Y – 4, or Y – 5 in the nearby connection. The most common “classic” case is a Δ4 Tyr corner (more than 40 examples listed), in which the H bond is to residue Y – 4 and the Tyr x1 is near −60°. Y – 2 is almost always a glycine, whose left-handed β or very extended β conformation helps the backbone curve around the Tyr ring. Residue Y – 3 is in polyproline II conformation (often Pro), and residue Y – 5 is usually a hydrophobic (often Leu) that packs next to the Tyr ring. The consensus sequence, then, is LxPGxY, where the first x (the H-bonding position) is hydrophilic. Residues Y and Y – 2 both form narrow pairs of β-sheet H-bonds with the neighboring strand, Δ5 Tyr corners have a 1-residue insertion between the Gly and the Tyr, forming a β-bulge. One protein family has a Δ4 corner formed by a His rather than a Tyr, and several examples use Trp in place of Tyr. For almost all these cases, the protein or domain is a Greek key β-barrel structure, the Tyr corner ends a Greek key connection, and it is well-conserved in related proteins. Most low-twist Greek key β-barrels have 1 Tyr corner. “Reverse” Δ4 Tyr corners (H bonded to Y + 4) and other variants are described, all less common and less conserved. It seems likely that the more classic Tyr corners (Δ4, Δ5, and Δ3 Tyr, Trp, or His) contribute to the stability of a Greek key connection over a hairpin connection, and also that they may aid in the process of folding up Greek key structures.