Amyloid particles facilitate surface-catalyzed cross-seeding by acting as promiscuous nanoparticles.

Autor:	Koloteva-Levine N; Kent Fungal Group, School of Biosciences, University of Kent, CT2 7NJ Canterbury, United Kingdom., Aubrey LD; Kent Fungal Group, School of Biosciences, University of Kent, CT2 7NJ Canterbury, United Kingdom., Marchante R; Kent Fungal Group, School of Biosciences, University of Kent, CT2 7NJ Canterbury, United Kingdom., Purton TJ; Kent Fungal Group, School of Biosciences, University of Kent, CT2 7NJ Canterbury, United Kingdom., Hiscock JR; School of Physical Sciences, University of Kent, CT2 7NJ Canterbury, United Kingdom., Tuite MF; Kent Fungal Group, School of Biosciences, University of Kent, CT2 7NJ Canterbury, United Kingdom., Xue WF; Kent Fungal Group, School of Biosciences, University of Kent, CT2 7NJ Canterbury, United Kingdom; w.f.xue@kent.ac.uk.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2021 Sep 07; Vol. 118 (36).
DOI:	10.1073/pnas.2104148118
Abstrakt:	Amyloid seeds are nanometer-sized protein particles that accelerate amyloid assembly as well as propagate and transmit the amyloid protein conformation associated with a wide range of protein misfolding diseases. However, seeded amyloid growth through templated elongation at fibril ends cannot explain the full range of molecular behaviors observed during cross-seeded formation of amyloid by heterologous seeds. Here, we demonstrate that amyloid seeds can accelerate amyloid formation via a surface catalysis mechanism without propagating the specific amyloid conformation associated with the seeds. This type of seeding mechanism is demonstrated through quantitative characterization of the cross-seeded assembly reactions involving two nonhomologous and unrelated proteins: the human Aβ42 peptide and the yeast prion-forming protein Sup35NM. Our results demonstrate experimental approaches to differentiate seeding by templated elongation from nontemplated amyloid seeding and rationalize the molecular mechanism of the cross-seeding phenomenon as a manifestation of the aberrant surface activities presented by amyloid seeds as nanoparticles. Competing Interests: The authors declare no competing interest. (Copyright © 2021 the Author(s). Published by PNAS.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu