Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Determinants of amyloid fibril degradation by the PDZ protease HTRA1

Poepsel, Simon, Sprengel, Andreas, Sacca, Barbara, Kaschani, Farnusch, Kaiser, Markus, Gatsogiannis, Christos, Raunser, Stefan, Clausen, Tim and Ehrmann, Michael ORCID: 2015. Determinants of amyloid fibril degradation by the PDZ protease HTRA1. Nature Chemical Biology 11 (11) , pp. 862-869. 10.1038/nchembio.1931

[thumbnail of Poepsel Nat Chem Biol 2015.pdf]
PDF - Submitted Pre-Print Version
Download (3MB) | Preview


Excessive aggregation of proteins has a major impact on cell fate and is a hallmark of amyloid diseases in humans. To resolve insoluble deposits and to maintain protein homeostasis, all cells use dedicated protein disaggregation, protein folding and protein degradation factors. Despite intense recent research, the underlying mechanisms controlling this key metabolic event are not well understood. Here, we analyzed how a single factor, the highly conserved serine protease HTRA1, degrades amyloid fibrils in an ATP-independent manner. This PDZ protease solubilizes protein fibrils and disintegrates the fibrillar core structure, allowing productive interaction of aggregated polypeptides with the active site for rapid degradation. The aggregate burden in a cellular model of cytoplasmic tau aggregation is thus reduced. Mechanistic aspects of ATP-independent proteolysis and its implications in amyloid diseases are discussed.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Additional Information: PDF uploaded in accordance with publisher's policies at (accessed 11.02.16).
Publisher: Nature Publishing Group
ISSN: 1552-4450
Date of Acceptance: 9 September 2015
Last Modified: 06 Nov 2023 21:32

Citation Data

Cited 68 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item


Downloads per month over past year

View more statistics