STRUCTURE AND EVOLUTION OF PARALLEL BETA-HELIX PROTEINS

Three bacterial pectate lyases, a pectin lyase from Aspergillus niger, the structures of rhamnogalacturonase A from Aspergillus aculeatus, R Gase A, and the P22-phage tailspike protein, TSP, display the right-ha nded parallel beta-helix architecture first seen in pectate lyase. The lyases have 7 complete coils while RGase A and TSP have 11 and 12, re spectively. Each coil contains three beta-strands and three turn regio ns named PB1, T1, PB2, T2, PB3, and T3 in their order of occurrence. T he lyases have homologous sequences but RGase A and TSP do not show ob vious sequence homology either to the lyases or to each other. However the structural similarities between all these molecules are so extens ive that divergence from a common ancestor is much more probable than convergence to the same fold, The region PB2-T2-PB3 is the best conser ved region in the lyases and shows the dearest structural similarity. Not only is the pleating and the direction of the hydrogen bonding in the sheets conserved, but so is the unusual alpha(L)-conformation turn between the two sheets, However, the overall shape, the position of l ong loops, a conserved alpha-helix that covers the amino-terminal end of the parallel beta-helix and stacks of residues in alpha(R)-conforma tion at the start of PB1 all suggest a common ancestor, The functional similarity, that the enzymes all bind alpha-galactose containing poly mers at an equivalent site involving PB1 and its two flanking turn reg ions, further supports divergent evolution. We suggest that the stacki ng of the coils and the unusual near perpendicular junction of PB2 and PB3 make the parallel beta-helix fold especially likely to maintain s imilar main chain conformations during divergent evolution even after all vestige of similarity in primary structure has vanished (C) 1998 A cademic Press.