Domain swapping in p13suc1 results in formation of native-like, cytotoxic aggregates |
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Authors: | Rousseau Frederic Wilkinson Hannah Villanueva Josep Serrano Luis Schymkowitz Joost W H Itzhaki Laura S |
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Institution: | SWITCH Laboratory, Flanders Institute for Biotechnology (VIB), Free University of Brussels, Pleinlaan 2, 1050 Brussels, Belgium. |
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Abstract: | The field of protein aggregation has been occupied mainly with the study of beta-strand self-association that occurs as a result of misfolding and leads to the formation of toxic protein aggregates and amyloid fibers. However, some of these aggregates retain native-like structural and enzymatic properties suggesting mechanisms other than beta-strand assembly. p13suc1 is a small protein that can exist as a monomer or a domain-swapped dimer. Here, we show that, under native conditions, p13suc1 forms three-dimensional domain-swapped aggregates, and that these aggregates are cytotoxic. Thus, toxicity of protein aggregates is not only associated with beta-rich assemblies and amyloid fibers, involving non-native interactions, but it can be induced by oligomeric misassembly that maintains predominantly native-like interactions. |
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Keywords: | MALDI-TOF matrix-assisted laser desorption/ionization time-of-flight |
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