Volume 16, Issue 26 p. 7881-7888
Full Paper

How Post-Translational Modifications Influence Amyloid Formation: A Systematic Study of Phosphorylation and Glycosylation in Model Peptides

Malgorzata Broncel

Malgorzata Broncel

Institut für Chemie und Biochemie, Freie Universität Berlin, Takustrasse 3, 14195 Berlin (Germany), Fax: (+49) 30-838-55644

These authors contributed equally to this work.

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Jessica A. Falenski

Jessica A. Falenski

Institut für Chemie und Biochemie, Freie Universität Berlin, Takustrasse 3, 14195 Berlin (Germany), Fax: (+49) 30-838-55644

These authors contributed equally to this work.

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Sara C. Wagner Dr.

Sara C. Wagner Dr.

Institut für Chemie und Biochemie, Freie Universität Berlin, Takustrasse 3, 14195 Berlin (Germany), Fax: (+49) 30-838-55644

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Christian P. R. Hackenberger Dr.

Christian P. R. Hackenberger Dr.

Institut für Chemie und Biochemie, Freie Universität Berlin, Takustrasse 3, 14195 Berlin (Germany), Fax: (+49) 30-838-55644

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Beate Koksch Prof. Dr.

Beate Koksch Prof. Dr.

Institut für Chemie und Biochemie, Freie Universität Berlin, Takustrasse 3, 14195 Berlin (Germany), Fax: (+49) 30-838-55644

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First published: 05 July 2010
Citations: 31

Graphical Abstract

All against amyloid formation: An important step towards the understanding of the impact of phosphorylation and glycosylation on amyloid formation has been made (see figure). It has been demonstrated that even single phosphorylation is sufficient to completely inhibit fibrilization, whereas glycosylation showed more diverse effects.

Abstract

A reciprocal relationship between phosphorylation and O-glycosylation has been reported for many cellular processes and human diseases. The accumulated evidence points to the significant role these post-translational modifications play in aggregation and fibril formation. Simplified peptide model systems provide a means for investigating the molecular changes associated with protein aggregation. In this study, by using an amyloid-forming model peptide, we show that phosphorylation and glycosylation can affect folding and aggregation kinetics differently. Incorporation of phosphoserines, regardless of their quantity and position, turned out to be most efficient in preventing amyloid formation, whereas O-glycosylation has a more subtle effect. The introduction of a single β-galactose does not change the folding behavior of the model peptide, but does alter the aggregation kinetics in a site-specific manner. The presence of multiple galactose residues has an effect similar to that of phosphorylation.