Biochemical and aggregation analysis of Bence Jones proteins from different light chain diseases
Biochemical and aggregation analysis of Bence Jones proteins from different light chain diseases
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DOI：
10.1080/13506120701815324
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发表时间：
2008-01-01
影响因子：
5.5
通讯作者：
Ramirez-Alvarado, Marina
中科院分区：
文献类型：
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作者：
Sikkink, Laura A.;Ramirez-Alvarado, Marina
免疫球蛋白轻链的沉积是分泌游离免疫球蛋白轻链（也称为Bence Jones蛋白（BJP））的单克隆浆细胞克隆增殖的结果。这些BJP大量存在于循环中，并在各种轻链疾病如轻链淀粉样变性（AL）、轻链沉积病（LCDD）和多发性骨髓瘤（MM）中经尿液排泄。从AL、LCDD和MM患者的尿液中纯化BJP，并进行研究以确定其二级结构、热力学稳定性和聚集体形成动力学。我们的研究结果表明，LCDD和MM蛋白质具有最低的折叠自由能，而所有的蛋白质显示出相似的熔化温度。BJP在其熔化温度下孵育产生形态上不同的聚集体：来自AL蛋白的淀粉样纤维、来自LCDD蛋白的无定形聚集体和来自MM蛋白的大球形物质。在体外条件下形成的聚集体表明，来自不同轻链疾病患者的各种蛋白质可能遵循不同的聚集途径。
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.