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.

Torches, Candles, Lamps, Lanterns, Flashlights, Spotlights, Night Vision Goggles… You Need Them All to See in Darkness

“…Among many other interesting observations, this analysis revealed that the BHRs of porins share high level of sequence similarity with β‐arcade motifs. This finding provided a mechanistic explanation for the ability of some amyloidogenic sequence to fold in either the ring‐like shape oligomers or elongated amyloid fibrils …”

“…[14] Based on the premises that many β-hairpin repeat (BHR) structures have cross-β arrangement typically found in amyloid fibrils, Villain et al analyzed the relationship between the amino acid sequences of the β-hairpin structures and amyloidogenic βarcade-forming motifs. [16] To this end, they conducted a comprehensive bioinformatics analysis of BHR structures in order to find if they contain amylodogenic motifs able to form β-arcade fibrils. [16] Among many other interesting observations, this analysis revealed that the BHRs of porins share high level of sequence similarity with β-arcade motifs.…”

“…[16] To this end, they conducted a comprehensive bioinformatics analysis of BHR structures in order to find if they contain amylodogenic motifs able to form β-arcade fibrils. [16] Among many other interesting observations, this analysis revealed that the BHRs of porins share high level of sequence similarity with β-arcade motifs. This finding provided a mechanistic explanation for the ability of some amyloidogenic sequence to fold in either the ring-like shape oligomers or elongated amyloid fibrils.…”

“…This finding provided a mechanistic explanation for the ability of some amyloidogenic sequence to fold in either the ring-like shape oligomers or elongated amyloid fibrils. [16] Deryusheva et al [17] conducted an analysis of the DisProt database (http://www.disprot.org/), [18] to evaluate the prevalence of lipid-binding IDPs (LBIDPs). This analysis showed that at least 15% of experimentally validated IDPs are able to bind lipids, and these LBIDPs were grouped into four classes based on their conformational state, domain structure, functional categories, and ligand type.…”

Amyloid and Amyloid-Like Aggregates: Diversity and the Term Crisis

“…However, there is a possibility that it could be widespread. Bioinformatic analysis suggested that the porin fragments forming the inner part of the pore were capable of forming amyloid structures [194].…”