Porins and Amyloids are Coded by Similar Sequence Motifs

Abstract

The relationship between amino acid sequences of the β-hairpin structures and amyloidogenic β-arcade-forming motifs are of special interest because, similar to amyloid fibrils, most of the β-hairpin repeat (BHR) structures have the so-called cross-β arrangement. Moreover, β-hairpin is considered as a probable intermediate structure in amyloidogenesis. In this work, a bioinformatics sequence analysis of the known BHR structures is performed in search of amylodogenic motifs able to form β-arcade fibrils. The analysis shows that the occurrence of the predicted β-arcade motifs in the BHR regions is very different depending on the BHR structural fold, cellular localization, and phylogeny. One of the most striking observations is the high level of sequence similarity between the BHRs of membranous porins and β-arcade motifs. This sequence similarity provides additional evidence that the structure of the membranous porins and annular amyloid oligomers may bear a resemblance. Moreover, these results explain how some amyloidogenic sequence can fold in either the ring-like shape oligomers or elongated amyloid fibrils. It has been also found that potentially lethal amyloidogenic β-arcade motifs are absent in the elongated BHR structures of intracellular eukaryotic proteins. It allows to hypothesize that, in this case, the selective evolutionary pressure acts against aggregation.

Keywords: aggregation; amyloid oligomer; bacterial porin; bioinformatics; evolution.