title: A comprehensive analysis of the Greek key motifs in protein beta-barrels and beta-sandwiches.
abstract: The Greek key motifs are the topological signature of many beta-barrels and a majority of beta-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 beta-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 beta-barrel structures analyzed here, half have left-handed Greek keys. This result challenges the empirical claim of the handedness regularity of Greek keys in beta-barrels. One of the five-stranded topologies that has not been observed in beta-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 beta-sandwich structures. Using this unit as the root, we have built a new taxonomy tree for the beta-sandwich folds and deduced a set of rules that appear to constrain how other beta-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 beta-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. Proteins 2000;40:409-419.
authors.affiliation: Department of Chemistry and E.O. Lawrence Berkeley National Laboratory University of California, Berkeley, California.
authors.forename: C
authors.initials: C
authors.lastname: Zhang
authors.forename: S H
authors.initials: SH
authors.lastname: Kim
mesh_terms: D020816:Amino Acid Motifs; D016208:Databases, Factual; D006860:Hydrogen Bonding; D008958:Models, Molecular; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D020539:Sequence Analysis, Protein