Dynamics of oligomer and amyloid fibril formation by yeast prion Sup35 observed by high-speed atomic force microscopy

How prion proteins stack up

31 August 2020

An imaging study of prion formation in yeast could help explain how misfolded proteins aggregate in human diseases such as Alzheimer’s.

Misfolded proteins known as prions can cause fatal infections in people and animals and are associated with various neurodegenerative diseases.

A team from Japan used advanced microscopy techniques developed at Kanazawa University to visualize the process by which individual prion proteins in yeast combine to form highly ordered fibrils — all at high resolution and in real time.

The researchers found that longer incubation times were needed for individual prions to fashion themselves into fibrils, with their orderly stacked-sheet arrangement, instead of into messier, clump-like structures called oligomers.

Fibril building occurred through gradual incorporation of individual prions, not through the addition of oligomers, which are kept away from fibrils through the repulsive forces. Blocking this fibril-elongation process could help treat a range of prion-associated diseases.

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References

1. PNAS 117, 7831–7836 (2020). doi: 10.1073/pnas.1916452117