Abstract

Single particle electron microscopy and electron tomography have been used to study models of protein misfolding, aggregation, and disaggregation. Using a yeast aggregation models, we are examining the structure of amyloid and other deposits in situ. For a yeast [PSI+] prion model, we examined how the deposits depend on the Hsp70 chaperone system. The expression of individual components of the Hsp70 system was manipulated to probe their actions in determining the balance between amyloid fibril assembly and disassembly. By an in vitro approach, we have also imaged the mammalian Hsp70 chaperone machinery during disassembly of amyloid fibrils.

References

Carroni, M, Kummer, E, Oguchi, Y, Wendler, P, Clare, DK, Sinning, I, Kopp, J, Mogk, A, Bukau, B, Saibil, H (2014) Head-to-tail interactions of the coiled-coil domains regulate ClpB cooperation with Hsp70 in protein disaggregation. eLife 3:e02481

O’Driscoll, J, Clare, DK, Saibil, HR (2015) Remodelling of prion aggregates in yeast cells by the Hsp104-Hsp110 disaggregase machinery. J. Cell Biol. 211, 145-158.

Gao, X Carroni, M, Nussbaum-Krammer, C, Mogk, A, Nillegoda, NB, Szlachcic, A, Guilbride, DL, Saibil, HR, Mayer, MP and Bukau, B (2015) Human Hsp70 disaggregase reverses Parkinson’s-linked α-synuclein amyloid fibrils. Molec. Cell 59, 781-793.

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