Structural architecture of amyloid-β oligomers, curvilinear protofibrils and annular assemblies, imaged by cryo-EM and cryo-ET

Liang, R.; Torres-Flores, A. P.; Qi, S.; Khursheed, A.; Tian, Y.; Szwedziak, P.; Baker, M. D.; Volkov, V. A.; Darbari, V. C.; Viles, J. H.

doi:10.1101/2024.03.01.582902

bioRxiv · 10.1101/2024.03.01.582902

Structural architecture of amyloid-β oligomers, curvilinear protofibrils and annular assemblies, imaged by cryo-EM and cryo-ET

Liang, R.·Torres-Flores, A. P.·Qi, S.·Khursheed, A.·Tian, Y.·Szwedziak, P.·Baker, M. D.·Volkov, V. A.·Darbari, V. C.·Viles, J. H.

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Abstract

Small prefibrillar structures of the amyloid-{beta} peptide (A{beta}) are believed to be central to cytotoxicity in Alzheimers disease, the most common form of dementia. A snapshot of these prefibrillar assemblies has therefore been characterized using a combination of cryo-ET and cryo-EM single particle analysis. This has facilitated an understanding of the relationship between, oligomers, curvilinear protofibrils and annular assemblies. A highly consistent diameter for all curvilinear protofibrils and oligomers of 28 [A], indicates that these assemblies are simply structural extensions from the smaller oligomers. Furthermore, their basic crosssection suggests mature amyloid fibrils might be initiated by the lateral binding of two curvilinear protofibrils. Ab-initio 3D reconstruction also reveals ring-shaped annular assemblies. These possess a central internal channel, ca. 14 [A] in diameter and 54 [A] long, which is capable of traversing lipid membranes. Large conductance recorded using patch-clamp electrophysiology, match the internal diameter of the A{beta} annular architecture.

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Liang, R., Torres-Flores, A. P., Qi, S., Khursheed, A., Tian, Y., Szwedziak, P., Baker, M. D., Volkov, V. A., Darbari, V. C., Viles, J. H.. 2024-03-03. Structural architecture of amyloid-β oligomers, curvilinear protofibrils and annular assemblies, imaged by cryo-EM and cryo-ET. https://doi.org/10.1101/2024.03.01.582902

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