Biochemical and aggregation analysis of Bence Jones proteins from different light chain diseases

被引：37

作者：

Sikkink, Laura A. ^{[1
]}

Ramirez-Alvarado, Marina ^{[1
]}

机构：

[1] Mayo Clin Coll Med, Dept Biochem & Mol Biol, Rochester, MN 55905 USA

来源：

AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS | 2008年 / 15卷 / 01期

关键词：

light chain amyloidosis; light chain deposition disease; multiple myeloma; circular dichroism; electron microscopy; fibrils; aggregates; amyloid;

D O I：

10.1080/13506120701815324

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Deposition of immunoglobulin light chains is a result of clonal proliferation of monoclonal plasma cells that secrete free immunoglobulin light chains, also called Bence Jones proteins (BJP). These BJP are present in circulation in large amounts and excreted in urine in various light chain diseases such as light chain amyloidosis (AL), light chain deposition disease (LCDD) and multiple myeloma (MM). BJP from patients with AL, LCDD and MM were purified from their urine and studies were performed to determine their secondary structure, thermodynamic stability and aggregate formation kinetics. Our results show that LCDD and MM proteins have the lowest free energy of folding while all proteins show similar melting temperatures. Incubation of the BJP at their melting temperature produced morphologically different aggregates: amyloid fibrils from the AL proteins, amorphous aggregates from the LCDD proteins and large spherical species from the MM proteins. The aggregates formed under in vitro conditions suggested that the various proteins derived from patients with different light chain diseases might follow different aggregation pathways.

引用

页码：29 / 39

页数：11

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