[NMR paper] Expanding the Repertoire of Amyloid Polymorphs by Co-polymerization of Related Protein Precursors.

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Expanding the Repertoire of Amyloid Polymorphs by Co-polymerization of Related Protein Precursors.

Related Articles Expanding the Repertoire of Amyloid Polymorphs by Co-polymerization of Related Protein Precursors.

J Biol Chem. 2013 Jan 17;

Authors: Sarell CJ, Woods LA, Su Y, Debelouchina GT, Ashcroft AE, Griffin RG, Stockley PG, Radford SE

Abstract
Amyloid fibrils can be generated from proteins with diverse sequences and folds. While amyloid fibrils assembled in vitro commonly involve a single protein precursor, fibrils formed in vivo can contain more than one protein sequence. How fibril structure and stability differ in fibrils composed of single proteins (homopolymeric fibrils) from those generated by co-polymerization of more than one protein sequence (heteropolymeric fibrils), is poorly understood. Here we compare the structure and stability of homo and heteropolymeric fibrils formed from human ?2-microglobulin and its truncated variant ?N6. We use an array of approaches (limited proteolysis, magic angle spinning NMR, Fourier transform infrared spectroscopy and fluorescence) combined with measurements of thermodynamic stability to characterize the different fibril types. The results reveal fibrils with different structural properties, different sidechain packing and strikingly different stabilities. These findings demonstrate how co-polymerization of related precursor sequences can expand the repertoire of structural and thermodynamic polymorphism in amyloid fibrils, to an extent that is greater than that obtained by polymerization of a single precursor alone.


PMID: 23329840 [PubMed - as supplied by publisher]



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