Analysis of the sequence and structural features of the left-handed beta-helical fold.

The left-handed parallel beta-helix (LbetaH) is a structurally repetitive, highly regular, and symmetrical fold formed by coiling of elongated beta-sheets into helical "rungs." This canonical fold has recently received interest as a possible solution to the fibril structure of amyloid and as a building block of self-assembled nanotubular structures. In light of this interest, we aimed to understand the structural requirements of the LbetaH fold. We first sought to determine the sequence characteristics of the repeats by analyzing known structures to identify positional preferences of specific residues types. We then used molecular dynamics simulations to demonstrate the stabilizing effect of successive rungs and the hydrophobic core of the LbetaH. We show that a two-rung structure is the minimally stable LbetaH structure. In addition, we defined the structure-based sequence preference of the LbetaH and undertook a genome-wide sequence search to determine the prevalence of this unique protein fold. This profile-based LbetaH search algorithm predicted a large fraction of LbetaH proteins from microbial origins. However, the relative number of predicted LbetaH proteins per specie was approximately equal across the genomes from prokaryotes to eukaryotes.