Abstract：
: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.
journal_name
Nat Chem Bioljournal_title
Nature chemical biologyauthors
Poepsel S,Sprengel A,Sacca B,Kaschani F,Kaiser M,Gatsogiannis C,Raunser S,Clausen T,Ehrmann Mdoi
10.1038/nchembio.1931subject
Has Abstractpub_date
2015-11-01 00:00:00pages
862-9issue
11eissn
1552-4450issn
1552-4469pii
nchembio.1931journal_volume
11pub_type
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