SERF protein is a direct modifier of amyloid fiber assembly
| Autor: | S Fabio, Falsone, N Helge, Meyer, Evelyne, Schrank, Gerd, Leitinger, Chi L L, Pham, Michelle T, Fodero-Tavoletti, Mats, Holmberg, Martin, Dulle, Benjamin, Scicluna, Bernd, Gesslbauer, Hanna-Marie, Rückert, Gabriel E, Wagner, David A, Merle, Ellen A, Nollen, Andreas J, Kungl, Andrew F, Hill, Roberto, Cappai, Klaus, Zangger |
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| Rok vydání: | 2011 |
| Předmět: | |
| Zdroj: | Cell Reports |
| ISSN: | 2211-1247 |
| Popis: | Summary The inherent cytotoxicity of aberrantly folded protein aggregates contributes substantially to the pathogenesis of amyloid diseases. It was recently shown that a class of evolutionary conserved proteins, called MOAG-4/SERF, profoundly alter amyloid toxicity via an autonomous but yet unexplained mode. We show that the biological function of human SERF1a originates from its atypical ability to specifically distinguish between amyloid and nonamyloid aggregation. This inherently unstructured protein directly affected the aggregation kinetics of a broad range of amyloidogenic proteins in vitro, while being inactive against nonamyloid aggregation. A representative biophysical analysis of the SERF1a:α-synuclein (aSyn) complex revealed that the amyloid-promoting activity resulted from an early and transient interaction, which was sufficient to provoke a massive increase of soluble aSyn amyloid nucleation templates. Therefore, the autonomous amyloid-modifying activity of SERF1a observed in living organisms relies on a direct and dedicated manipulation of the early stages in the amyloid aggregation pathway. Graphical Abstract Highlights ► SERF1a drives the assembly of amyloidogenic proteins ► SERF1a discriminates between amyloid and nonamyloid aggregation ► SERF1a acts through an early interaction with α-synuclein amyloid precursors ► SERF1a catalyzes the formation of transient α-synuclein “on-pathway” aggregates The protein class called MOAG-4/SERF profoundly alters amyloid protein toxicity via an autonomous and previously unidentified pathway. Falsone and colleagues demonstrate that the amyloid-modifying ability of human SERF1a is driven by a transient interaction with early precursors in the amyloid pathway. As a consequence, SERF1a promotes amyloid aggregation of several amyloidogenic proteins, while being insensitive to unspecific protein aggregation. This identifies SERF1as a specialized amyloid factor, in support to its autonomous mode of action observed in cells. |
| Databáze: | OpenAIRE |
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