Recovery of functional enzyme from amyloid fibrils

Agócs, Gergely; Solymosi, Katalin; Varga, Andrea; Módos, Károly; Kellermayer, Miklós; Závodszky, Péter; Fidy, Judit; Osváth, Szabolcs

doi:10.1016/j.febslet.2010.01.058

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Volume 584, Issue 6 , Pages 1139-1142, 19 March 2010

Recovery of functional enzyme from amyloid fibrils

Edited by Jesus Avila

Gergely Agócs
- Department of Biophysics and Radiation Biology, Semmelweis University, Tűzoltó u. 37-47, H-1094 Budapest, Hungary
Katalin Solymosi
- Department of Plant Anatomy, Eötvös Loránd University, Pázmány Péter s. 1/C, H-1117 Budapest, Hungary
Andrea Varga
- Institute of Enzymology, Biological Research Center, Karolina út 29, H-1113 Budapest, Hungary
Károly Módos
- Department of Biophysics and Radiation Biology, Semmelweis University, Tűzoltó u. 37-47, H-1094 Budapest, Hungary
Miklós Kellermayer
- Department of Biophysics and Radiation Biology, Semmelweis University, Tűzoltó u. 37-47, H-1094 Budapest, Hungary
Péter Závodszky
- Institute of Enzymology, Biological Research Center, Karolina út 29, H-1113 Budapest, Hungary
Judit Fidy
- Department of Biophysics and Radiation Biology, Semmelweis University, Tűzoltó u. 37-47, H-1094 Budapest, Hungary
Szabolcs Osváth
- Department of Biophysics and Radiation Biology, Semmelweis University, Tűzoltó u. 37-47, H-1094 Budapest, Hungary
- Corresponding author. Fax: +36 1 266 6656.

Received 9 November 2009; received in revised form 27 January 2010; accepted 28 January 2010. published online 02 February 2010.

Abstract

Amyloid deposits, which accumulate in numerous diseases, are the final stage of multi-step protein conformational-conversion and oligomerization processes. The underlying molecular mechanisms are not fully understood, and particularly little is known about the reverse reaction. Here we show that phosphoglycerate kinase amyloid fibrils can be converted back into native protein. We achieved recovery with 60% efficiency, which is comparable to the success rate of the unfolding-refolding studies, and the recovered enzyme was folded, stable and fully active. The key intermediate stages in the recovery process are fibril disassembly and unfolding followed by spontaneous protein folding.

Abbreviations: PGK, yeast (Saccharomyces cerevisiae) phosphoglycerate kinase, 3-PG, 3-phosphoglycerate

Keywords: Protein aggregation, Amyloid, Refolding, Enzyme activity