Functional amyloid fibrils from fungi and viruses

This talk focuses on Functional Amyloid Fibrils from Fungi and Viruses. The structures of these fibrils and how the unique amyloid structure gives rise to biological functions. I'm Margaret Sunde, a Professor in Molecular Biomedicine from the University of Sydney in Australia.

The talk is in three main parts. Firstly, I will discuss what amyloid fibrils are, and the similarities and differences between amyloid fibrils associated with diseases or pathology and those amyloid fibrils which have distinct biological roles or activities. In the second part, I'll focus on one type of functional amyloid produced by filamentous fungi. These are fibrils composed of fungal proteins known as hydrophobins. I will explain what we know about their structure, how these fibrils form, and provide an example of how they impact human health. In the final section, I will explain the role that functional amyloid fibrils play in mammalian cell death pathways. I will show you how certain viral proteins that can form amyloid fibrils are able to inhibit the host's innate response to viral infection.

What do we mean by amyloid fibrils? Insoluble fibrillar protein deposits were first described in association with human disease in the 1800s. Since the early 2000s, protein fibrils with similar structures have been identified in organisms across the tree of life including bacteria, viruses, fungi, plants, and mammals. Where these fibrils are not associated with any disease but they do have biological functions. In both disease-associated and natural or functional fibrils, the precursor proteins which polymerize to form the fibrils have a wide range of sizes, structures, and sequences. However, when these diverse proteins polymerize to form protein amyloid fibrils, the fibrils all exhibit common structural, tinctorial: that is how they stain, and morphological features. These can be considered the defining characteristics of amyloid and I'll illustrate these here. To start with, they are all generally long, straight, and unbranching, and approximately ten nanometers wide. You can see them in this electron micrograph here. A good example of amyloid fibrils. All amyloid fibrils also stain in a characteristic way with the dyes Congo red and Thioflavin T. Here I've illustrated an amyloid deposit stained with Congo red. In the bright field image on the left, you can see the uptake of the red dye. However, when this is viewed between cross-polarizers, the amyloid deposits appear with green birefringence due to the preferential ordering of the di-molecules along the long amyloid fibrils. Finally, all amyloid fibrils exhibit a similar cross-β X-ray fiber diffraction pattern, indicating that they all have a similar underlying molecular scaffold. The X-ray fiber diffraction pattern is illustrated on the bottom right. It consists of two major reflections, a strong 4.8 angstrom meridional reflection that comes from a regular spacing along the fibril's long axis. In the cartoon, you can see that this 4.8 Angstrom spacing comes from the distance between β-strands in the direction of intrastrand hydrogen bonding. A weaker and more diffuse equatorial spacing lies at right angles to this, and is 8 to 12 angstroms. This comes from a more variable inter-sheet distance. Together these make up a β-sheet rich, poor architecture that is shared by all amyloid fibrils.