Effect of Lysine Modification on the Stability and Cellular Binding of Human Amyloidogenic Light Chains
Journal Article
·
· Biochimica et Biophysica Acta (BBA) - Biomembranes
OSTI ID:1000715
- ORNL
- University of Tennessee Graduate School of Medicine
AL amyloidosis is characterized by the pathologic deposition as fibrils of monoclonal light chains (i.e., Bence Jones proteins [BJPs]) in particular organs and tissues. This phenomenon has been attributed to the presence in amyloidogenic proteins of particular amino acids that cause these molecules to become unstable, as well as post-translational modifications and, in regard to the latter, we have investigated the effect of biotinylation of lysyl residues on cell binding. We utilized an experimental system designed to test if BJPs obtained from patients with AL amyloidosis or, as a control, multiple myeloma (MM), bound human fibroblasts and renal epithelial cells. As documented by fluorescent microscopy and ELISA, the amyloidogenic BJPs, as compared with MM components, bound preferentially and this reactivity increased significantly after chemical modification of their lysyl residues with sulfo-NHS-biotin. Further, based on tryptophan fluorescence and circular dichorism data, it was apparent that their conformation was altered, which we hypothesize exposed a binding site not accessible on the native protein. The results of our studies indicate that post-translational structural modifications of pathologic light chains can enhance their capacity for cellular interaction and thus may contribute to the pathogenesis of AL amyloidosis and multiple myeloma.
- Research Organization:
- Oak Ridge National Laboratory (ORNL)
- Sponsoring Organization:
- SC USDOE - Office of Science (SC)
- DOE Contract Number:
- AC05-00OR22725
- OSTI ID:
- 1000715
- Journal Information:
- Biochimica et Biophysica Acta (BBA) - Biomembranes, Journal Name: Biochimica et Biophysica Acta (BBA) - Biomembranes Journal Issue: 1 Vol. 1812; ISSN BBBMBS; ISSN 0304-4157
- Country of Publication:
- United States
- Language:
- English
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