Prediction of Transmembrane Regions, Cholesterol, and Ganglioside Binding Sites in Amyloid-Forming Proteins Indicate Potential for Amyloid Pore Formation

Besides amyloid fibrils, pores (APs) represent another mechanism of induced toxicity. Since hypothesis put forward by Arispe and collegues in 1993 that amyloid-beta makes ion-conducting channels Alzheimer's disease may be due to the toxic effect these channels, many studies have confirmed APs are formed prefibrillar oligomers amyloidogenic proteins a common source cytotoxicity. The pore formation is still not well-understood structure imaging living cells remains an open issue. To get closer understand AP we used predictive methods assess propensity set 30 amyloid-forming (AFPs) form transmembrane channels. A range amino-acid sequence tools were applied predict domains AFPs, provided context on future experiments needed order contribute toward deeper understanding In AFPs predicted their propensity, presence (TM) regions, cholesterol (CBM) ganglioside binding motifs (GBM), which likely bind. Noteworthy, all pathological share TM, CBM, GBM whereas functional amyloids seem show just one regions. For comparative purposes, also analyzed few examples behave as biologically non-relevant AFPs. Based known experimental data ?-amyloid ?-synuclein formation, suggest potential for formation. Oligomerization ?-TM helix ?-TM strands transition lipid rafts key events.