Molecular inscription of environmental information into protein suprastructures: temperature effects on unit assembly of α-synuclein oligomers into polymorphic amyloid fibrils

Abstract

Molecular-level storage of environmental information in biological structures in tangible forms, and their subsequent transfer to the next generation, has been studied using the phenomenon of amyloidogenesis, which defines a biochemical condition generating highly ordered protein aggregates known as amyloid fibrils. α-Synuclein oligomers shown to experience unit assembly as the formation of amyloid fibrils were used in the present study as an environment-sensing agent. With temperature varying in 2 °C intervals between 37 °C and 43 °C, the oligomeric unit assembly led to fibrillar polymorphism from a straight to a curly appearance, as assessed using TEM and small-angle neutron scattering; the different effects on the secondary structures were evaluated using attenuated total reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy. The resulting diversified amyloid fibrils, which have distinctive molecular characteristics, were shown to be inherited by the next generation through the self-propagating property of amyloidogenesis. Storage of intangible temperature information in the diversified protein suprastructures and perpetuation of the stored information in the form of polymorphic amyloid fibrils could represent molecular inscription of environmental information into biological systems; this could further extend our understanding of any physiological/pathological significance of amyloidogenic polymorphism and be utilized in the area of nanobiotechnology to process various external signals.

Morphological Evaluation of Meta-stable Oligomers of α-Synuclein with Small-Angle Neutron Scattering

“…The natively unfolded nature of αS capable of exhibiting structural plasticity upon its self-assembly and multiple partner interactions would be responsible for the multitude of αS oligomers and thus multiple pathways of the fibrillation 9 . We have studied one particular type of meta-stable αS oligomers (Meta-αS-Os) since they act as a growing unit to exhibit the accelerated amyloid fibril formation in the presence of external stimuli such as shear force 10 , temperature change 11 , pH 12 , and organic solvents 13 which are suspected to alter the structure of Meta-αS-Os into a self-associative state. In fact, this unit-assembly process was confirmed by producing the pea-pod type gold nanoparticle (AuNP) chain aligned within the protein nanofibril of αS from the αS-encapsulated AuNP units (αS-AuNP) in the presence of the stimuli including hexane or pH change 14 .…”

“…In fact, this unit-assembly process was confirmed by producing the pea-pod type gold nanoparticle (AuNP) chain aligned within the protein nanofibril of αS from the αS-encapsulated AuNP units (αS-AuNP) in the presence of the stimuli including hexane or pH change 14 . Meta-αS-Os were demonstrated to be a β-sheet free species whose global shape could be readily altered by the external influences for multiple assembly processes leading to the fibrillar polymorphism 11 . In addition, Meta-αS-Os were also shown to be a toxic membrane disrupting agent as they self-assembled into the radiating amyloid fibrils (RAFs) on the surface of liposomes 15 .…”

Stabilization Effect of Amino Acid Side Chains in Peptide Assemblies on Graphite Studied by Scanning Tunneling Microscopy

“…In addition to the effect of manipulating environmental conditions such as the surface support, pH and temperature, which can induce a peptide to adopt different conformations, the effect of sequence originates from the inherent properties of the polypeptide backbone and side chains . The hydrogen bonds between main chain carbonyl oxygen and amide nitrogen are crucial for assembly of peptides .…”

“…[8] Advances in theoretical and experimental efforts are key for furtheri nvestigating the effect of sequence on the binding interactions between variousamino acids and solid surfaces. [9] In addition to the effect of manipulating environmental conditions such as the surfaces upport, pH and temperature, which can induce ap eptide to adopt different conformations, [10] the effect of sequence originates from the inherent properties of the polypeptideb ackbonea nd side chains. [11] The hydrogen bonds betweenm ain chain carbonyl oxygen and amide nitrogen are crucial for assembly of peptides.…”

Looking at the recent advances in understanding α-synuclein and its aggregation through the proteoform prism

“…Slight changes in the environmental conditions during the fibrillation process were shown to cause the formation of morphologically different amyloid fibrils with distinctive molecular characteristics that can be inherited by the next generation of fibrils through self-propagation 175 . Under specific conditions, pure forms of structurally different fibrillar polymorphs of α-synuclein were obtained and characterized structurally and functionally 176 .…”