On the conformation of proteins: The handedness of the β-strand-α-helix-β-strand unit

Abstract

The β-strand-α-helix-β-strand unit consists of two parallel, but not necessarily adjacent, β-strands which lie in a β-pleated sheet and are connected by one or more α-helices. This unit, which occurs in 17 functionally different globular proteins, may adopt a right- or a left-handed conformation. An analysis of the distribution shows that 57 out of the 58 units are right-handed. If the unit had no right-handed preference, the probability of observing such a distribution by chance is 10 −16. This may be explained in terms of the twist of the β-sheet which is shown to favour a right-handed unit, as otherwise steric hindrance occurs in the loop regions. We show that the right-handed strand-helix-strand unit determines the sense of the super-secondary structure found in the dehydrogenases and of related folds found in other structures. The evolutionary relationships between proteins containing this unit are re-evaluated in terms of this preference. The high probability that the unit will fold with a right-handed conformation has implications for the prediction of tertiary structure.