A comprehensive analysis of the Greek key motifs in protein β-barrels and β-sandwiches

Abstract

The Greek key motifs are the topological signature of many β-barrels and a mojority of β-sandwich structures. An updated survey of these structures integrates many early observations and newly emerging patterns and provides a better understanding of the unique role of Greek keys in protein structures. A stereotypical Greek key β-barrel accommodates five or six strands and can have 12 possible topologies. All except one six-stranded topologies have been observed, and only one five-stranded topologies have been seen in actual structures. Of the representative β-barrel structures analyzed here, half have left-handed Greek keys. This result challenges the empirical claim of the handedness regularity of Greek keys in β-barrels. One of the five-stranded topologies that has not been observed in β-barrels comprises two overlapping Greek keys. The two three-dimensional forms of this topology constitute a structural unit that is present in a vast majority of known β-sandwich structures. Using this unit as the root, we have built a new taxonomy tree for the β-sandwich folds and deduced a set of rules that appear to constrain how other β-strands adjoin the unit to form a larger double-layered structure. These rules, though derived from a larger data set, are essentially the same as those drawn from earlier studies, suggesting that they may reflect the true topological constraints in the design of β-sandwich structures. Finally, a novel variant of the Greek key motif (defined here as the twisted Greek key) has emerged which introduces loop crossings into the folded structures. (C) 2000 Wiley-Liss, Inc.