The Hsc70 disaggregation machinery removes monomer units directly from α-synuclein fibril ends

Matthias M. Schneider; Saurabh Gautam; Therese W. Herling; Ewa Andrzejewska; Georg Krainer; Alyssa M. Miller; Victoria A. Trinkaus; Quentin A. E. Peter; Francesco Simone Ruggeri; Michele Vendruscolo; Andreas Bracher; Christopher M. Dobson; F. Ulrich Hartl; Tuomas P. J. Knowles

doi:10.1038/s41467-021-25966-w

Nature Communications (Oct 2021)

The Hsc70 disaggregation machinery removes monomer units directly from α-synuclein fibril ends

Matthias M. Schneider,
Saurabh Gautam,
Therese W. Herling,
Ewa Andrzejewska,
Georg Krainer,
Alyssa M. Miller,
Victoria A. Trinkaus,
Quentin A. E. Peter,
Francesco Simone Ruggeri,
Michele Vendruscolo,
Andreas Bracher,
Christopher M. Dobson,
F. Ulrich Hartl,
Tuomas P. J. Knowles

Affiliations

Matthias M. Schneider: Yusuf Hamied Department of Chemistry, Centre for Misfolding Diseases, University of Cambridge
Saurabh Gautam: Department of Cellular Biochemistry, Max-Planck Institute of Biochemistry
Therese W. Herling: Yusuf Hamied Department of Chemistry, Centre for Misfolding Diseases, University of Cambridge
Ewa Andrzejewska: Yusuf Hamied Department of Chemistry, Centre for Misfolding Diseases, University of Cambridge
Georg Krainer: Yusuf Hamied Department of Chemistry, Centre for Misfolding Diseases, University of Cambridge
Alyssa M. Miller: Yusuf Hamied Department of Chemistry, Centre for Misfolding Diseases, University of Cambridge
Victoria A. Trinkaus: Department of Cellular Biochemistry, Max-Planck Institute of Biochemistry
Quentin A. E. Peter: Yusuf Hamied Department of Chemistry, Centre for Misfolding Diseases, University of Cambridge
Francesco Simone Ruggeri: Yusuf Hamied Department of Chemistry, Centre for Misfolding Diseases, University of Cambridge
Michele Vendruscolo: Yusuf Hamied Department of Chemistry, Centre for Misfolding Diseases, University of Cambridge
Andreas Bracher: Department of Cellular Biochemistry, Max-Planck Institute of Biochemistry
Christopher M. Dobson: Yusuf Hamied Department of Chemistry, Centre for Misfolding Diseases, University of Cambridge
F. Ulrich Hartl: Department of Cellular Biochemistry, Max-Planck Institute of Biochemistry
Tuomas P. J. Knowles: Yusuf Hamied Department of Chemistry, Centre for Misfolding Diseases, University of Cambridge

DOI: https://doi.org/10.1038/s41467-021-25966-w
Journal volume & issue: Vol. 12, no. 1
pp. 1 – 11

Abstract

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Molecular chaperones from the Hsp70 family can break up protein aggregates, including amyloids. Here, the authors utilize microfluidic diffusional sizing to assess the mechanism of α-synuclein (αS) disaggregation by the Hsc70–DnaJB1–Apg2 system, and show that single αS molecules are removed directly from the fibril ends.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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