Title: Citrullination and deamidation affect aggregation properties of amyloid -proteins
Authors: Osaki, Dai
Hiramatsu, Hirotsugu
Department of Applied Chemistry
Keywords: Charge;oligomer;pH dependence;salt bridge;secondary structure
Issue Date: Dec-2016
Abstract: Citrullination and deamidation, which are aging-related posttranslational modifications, increase the number of negative charges on amyloid -protein (A) at neutral pH. We investigated the effects of these modifications on the fibrillation properties of A. The Arg5Cit modification of A(1-40) did not affect the fibrillation rate, and brought -sheet structures unlike that in the A(1-40) fibril. The Asn27Asp modification of A(1-40) stopped the fibrillation and induced the formation of aggregates that involved an anti-parallel -sheet. A(1-42) with the Arg5Cit modification showed increased solubility in aqueous media, and its fibril formation became slower than that of A(1-42). The modification did not change the parallel -sheet structure of the fibrils. A(1-42) with the Asn27Asp modification partially formed fibrils that involved the parallel -sheet structure. Using the thioflavin T (ThT) assay, an increased fraction of the soluble oligomer of each A analog was transiently detected during fibrillation. An increase in the number of negative charges at basic pH affected the aggregation properties of A in a manner different from that with the modifications, suggesting that change in properties of the posttanslationally modified residues rather than the number of charges in the peptide was important.
URI: http://dx.doi.org/10.1080/13506129.2016.1240076
ISSN: 1350-6129
DOI: 10.1080/13506129.2016.1240076
Volume: 23
Issue: 4
Begin Page: 234
End Page: 241
Appears in Collections:Articles