Back to Search Start Over

Non-fibrillar Components of Amyloid Deposits Mediate the Self-association and Tangling of Amyloid Fibrils.

Authors :
MacRaild, Christopher A.
Stewart, Cameron R.
Mok, Yee-Foong
Gunzburg, Menachem J.
Perugini, Matthew A.
Lawrence, Lynne J.
Tirtaatmadja, Viyada
Cooper-White, Justin J.
Howlett, Geoffrey J.
Source :
Journal of Biological Chemistry. 5/14/2004, Vol. 279 Issue 20, p21038-21045. 8p. 5 Graphs.
Publication Year :
2004

Abstract

Amyloid deposits are proteinaceous extra-cellular aggregates associated with a diverse range of disease states. These deposits are composed predominantly of amyloid fibrils, the unbranched, E-sheet rich structures that result from the misfolding and subsequent aggregation of many proteins. In addition, amyloid deposits contain a number of non-fibrillar components that interact with amyloid fibrils and are incorporated into the deposits in their native folded state. The influence of a number of the non-fibrillar components in amyloid-related diseases is well established; however, the mechanisms underlying these effects are poorly understood. Here we describe the effect of two of the most important non-fibrillar components, serum amyloid P component and apolipoprotein E, upon the solution behavior of amyloid fibrils in an in vitro model system. Using analytical ultracentrifugation, electron microscopy, and rheological measurements, we demonstrate that these non-fibrillar components cause soluble fibrils to condense into localized fibrillar aggregates with a greatly enhanced local density of fibril entanglements. These results suggest a possible mechanism for the observed role of non-fibrillar components as mediators of amyloid deposition and deposit stability. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00219258
Volume :
279
Issue :
20
Database :
Academic Search Index
Journal :
Journal of Biological Chemistry
Publication Type :
Academic Journal
Accession number :
13364177
Full Text :
https://doi.org/10.1074/jbc.M314008200