The architecture of parallel β-helices and related folds

Abstract

Three-dimensional structures have been determined of a large number of proteins characterized by a repetitive fold where each of the repeats (coils) supplies a strand to one or more parallel beta-sheets. Some of these proteins form superfamilies of proteins, which have probably arisen by divergent evolution from a common ancestor. The classical example is the family including four families of pectinases without obviously related primary sequences, the phage P22 tailspike endorhamnosidase, chrondroitinase B and possibly pertactin from Bordetella pertusis. These show extensive stacking of similar residues to give aliphatic, aromatic and polar stacks such as the asparagine ladder. This suggests that coils can be added or removed by duplication or deletion of the DNA corresponding to one or more coils and explains how homologous proteins can have different numbers of coils. This process can also account for the evolution of other families of proteins such as the beta-rolls, the leucine-rich repeat proteins, the hexapeptide repeat family, two separate families of beta-helical antifreeze proteins and the spiral folds. These families need not be related to each other but will share features such as relative untwisted beta-sheets, stacking of similar residues and turns between beta-strands of approximately 90 degrees often stabilized by hydrogen bonding along the direction of the parallel beta-helix.Repetitive folds present special problems in the comparison of structures but offer attractive targets for structure prediction. The stacking of similar residues on a flat parallel beta-sheet may account for the formation of amyloid with beta-strands at right-angles to the fibril axis from many unrelated peptides.

Evidence for assembly of prions with left-handed β-helices into trimers

“…Our finding on the residue distributions in left-handed and right-handed ␤-helices are in agreement with published studies (29,30).…”

“…Huntington's disease occurs when at least 36 consecutive glutamines are present in the polyglutamine region of huntingtin (55), which corresponds exactly to the number of residues needed to build two complete rungs of a left-handed ␤-helix. Asn stacks have been observed in parallel ␤-helices (30).…”

The crystal structure of filamentous hemagglutinin secretion domain and its implications for the two-partner secretion pathway

“…1). A coil corresponds to a complete turn of the parallel ␤-helix (22). This fold was first observed in pectate lyase C of E. chrysanthemi and 3.…”

“…1). The helix interior of Fha30 is essentially filled with stacks of aliphatic residues (by decreasing numbers Val, Leu, Ile, Ala, and Gly), as often observed in right-handed parallel ␤-helices (22). The ␤-turns and loops that link the ␤-strands, in general, contain one glycine residue and are in four of nine coils stabilized by hydrogen bonds between the coils main chain and the side chain of a serine residue pointing toward the ␤-helix interior (Fig.…”

The Biochemistry and Structural Biology of Plant Cell Wall Deconstruction

“…The structures of pectinases (polygalacturonases), pectate lyases, and pectin methylesterases have been extensively described and reviewed previously (Jenkins and Pickersgill, 2001). In general, these enzymes display a right-handed parallel b-helix topology.…”