Bio-nanoimaging

Bio-nanoimaging

Protein Misfolding and Aggregation
2014, Pages 247-254
Bio-nanoimaging

Chapter 22 - Imaging the Morphology and Structure of Apolipoprotein Amyloid Fibrils

https://doi.org/10.1016/B978-0-12-394431-3.00022-5Get rights and content

Abstract

Several plasma apolipoproteins are able to self-assemble into amyloid fibrils or influence amyloid fibril formation by other proteins. For instance, oxidation of methionine residues induces amyloid fibril formation by full-length apoA-I. ApoE is widely distributed in all types of amyloid plaques and forms amyloid-like fibrils. Specific isoforms of apoE are also genetically linked to the incidence of Alzheimer’s disease. ApoC-II forms fibrils under lipid-free conditions with a twisted ribbon-like morphology, and multiple physical techniques applied to the analysis of these fibrils have led to a structural model of individual subunits in a ‘G-like’ conformation, stacked in a linear array within the fibril. The size of apoC-II fibrils can be estimated using sedimentation velocity analysis, assuming that the fibrils conform to a flexible worm-like chain model. The concentration-dependent behavior of apoC-II fibrils is consistent with an equilibrium distribution of fibrils at low concentrations with evidence of irreversible fibril tangling at higher concentrations. In the presence of low concentrations of phospholipid micelles or bilayers, apoC-II self-associates to form fibrils with a distinct, rod-like morphology. The low conformational stability of lipid-deprived apolipoproteins may account for the high prevalence of plasma apolipoproteins in amyloid disease. In this chapter we review present knowledge of amyloid fibril formation by apolipoproteins obtained by various imaging techniques with specific reference to apolipoproteins (apo) A-I, E and C-II.

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  • Unique insights to intrinsically disordered proteins provided by ion mobility mass spectrometry

    2018, Current Opinion in Chemical Biology
    Citation Excerpt :

    Use of a toy model [39••] showed that α-synuclein explored approximately 90% of the collision cross section space available to it whilst ApoC-II only explored around 30%. An explanation for this anomalous result is that ApoC-II restructures as it desolvates, perhaps towards a helix rich structure akin to that in which it is found in membranes [53], or more likely to a well self-solvated compact globular state. Unlike structured proteins which can be characterised by wide CSDs when sprayed from solutions at low or high pH, ApoC-II shows little variation, which is also explained by restructuring upon transfer.

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