Sikkink Laura A, Ramirez-Alvarado Marina
Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Amyloid. 2008 Mar;15(1):29-39. doi: 10.1080/13506120701815324.
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.
免疫球蛋白轻链沉积是分泌游离免疫球蛋白轻链（也称为本-周蛋白，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；以及多发性骨髓瘤，MM）的尿液中排泄。从患有AL、LCDD和MM患者的尿液中纯化出BJP，并进行研究以确定其二级结构、热力学稳定性和聚集形成动力学。我们的结果表明，LCDD和MM蛋白具有最低的折叠自由能，而所有蛋白都显示出相似的解链温度。在其解链温度下孵育BJP会产生形态不同的聚集体：来自AL蛋白的淀粉样纤维、来自LCDD蛋白的无定形聚集体以及来自MM蛋白的大球形聚集体。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可能遵循不同的聚集途径。
Zotero 插件
