Annular oligomers

Concerning the nature and structure of such amyloid peptide or protein channels, oligomers with annular morphologies have in fact been observed by EM for a-synuclein (Lashuel et al., 2002) and equine lysozyme (Malisauskas et al., 2003) even in the absence of any lipids or membranes. Channel-like structures have also been reconstituted in liposomes and observed by SFM for A/ i 4o, A/ j 42, human amylin, a-synuclein, ABri, ADan, and serum amyloid A (Fig. 5A Lin et al., 2001 Quist et al., 2005). Doughnut-shaped structures with a diameter of 10-12 nm and a central hole size of 1-2 nm (Fig. 5B) were imaged on top of lipid membranes (Quist et al., 2005). However, the radius of curvature of the SFM tips meant that it is not possible to say whether the pores were really traversing the lipid bilayer. 

Oligomers with Four-Coordinate Annular Boron and Nitrogen... 

On one hand, it forms annular p-oligomers with a central channel-like pore that can perforate the plasma membrane of brain cells and affect Ca fluxes. On the other hand, the peptide can form p-rich protofibrils and fibrils. Kallberg et al. studied the propensity of various amyloid proteins to form either a or p secondary structures. They report the interesting observation that all amyloid proteins contain a/p discordant segments. These a/p discordant stretches correspond to a part of the protein that has been shown to adopt an a-helix structure in spite of being composed by amino acids that have a higher propensity... 

Alzheimer s, Parkinson s and prion diseases are characterized by neuronal loss and protein aggregates that may or may not be fibrillar. However, the exact identity of the neurotoxic species and the mechanism by which it kills neurons are unknown. Biophysical studies support the emerging notion that a prefibrillar oligomer (protofibril) may be responsible for cell death and that the fibrillar form that is typically observed post mortem may actually be neuroprotective. The laboratory of Peter Lansbury suggests that a subpopulation of the soluble protofibrils may function as pathogenic pores that might have the ability to permeabilize cell or mitochondrial membranes 35). Annular, pore-like structures are observed in familial mutants of a-synuclein (Parkinson s disease) and Alzheimer s precursor protein (Alzheimer s disease) as shown in Plate 3A 56). 

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