Acceleration of amyloid fibril formation by carboxyl-terminal truncation of human serum amyloid A

Copyright © 2017 Elsevier Inc. All rights reserved..

Human serum amyloid A (SAA) is a precursor protein of AA amyloidosis. Although the full-length SAA is 104 amino acids long, the C-terminal-truncated SAA lacking mainly residues 77-104 is predominantly deposited in AA amyloidosis. Nevertheless, the amyloid fibril formation of such truncated forms of human SAA has never been investigated. In the present study, we examined the effect of C-terminal truncation on amyloid fibril formation of human SAA induced by heparan sulfate (HS). Circular dichroism (CD) measurements demonstrated that the C-terminal truncation induces a reduced α-helical structure of the SAA molecule. HS-induced increases in thioflavin T fluorescence for SAA (1-76) peptide and less significant increases for full-length SAA were observed. CD spectral changes of SAA (1-76) peptide but not full-length SAA were observed when incubated with HS, although the spectrum was not typical for a β-structure. Fourier transform infrared experiments clearly revealed that SAA (1-76) peptide forms a β-sheet structure. Transmission electron microscopy revealed that short fibrillar aggregates of SAA (1-76) peptides, which became longer with increasing peptide concentrations, were observed under conditions in which full-length SAA scarcely formed fibrillar aggregates. These results suggested that the C-terminal truncation of human SAA accelerates amyloid fibril formation.

Medienart:

E-Artikel

Erscheinungsjahr:

2018

Erschienen:

2018

Enthalten in:

Zur Gesamtaufnahme - volume:639

Enthalten in:

Archives of biochemistry and biophysics - 639(2018) vom: 01. Feb., Seite 9-15

Sprache:

Englisch

Beteiligte Personen:

Tanaka, Masafumi [VerfasserIn]
Kawakami, Toru [VerfasserIn]
Okino, Nozomi [VerfasserIn]
Sasaki, Kaoru [VerfasserIn]
Nakanishi, Kiwako [VerfasserIn]
Takase, Hiroka [VerfasserIn]
Yamada, Toshiyuki [VerfasserIn]
Mukai, Takahiro [VerfasserIn]

Links:

Volltext

Themen:

9050-30-0
AA amyloidosis
Amyloid fibril
Carboxyl-terminal truncation
Heparitin Sulfate
Journal Article
Native chemical ligation
Protein Aggregates
Research Support, Non-U.S. Gov't
Serum Amyloid A Protein
Serum amyloid A

Anmerkungen:

Date Completed 14.02.2018

Date Revised 14.02.2018

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.abb.2017.12.016

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM279514247