scholarly journals Heterogeneity in Primary Structure, Post-Translational Modifications, and Germline Gene Usage of Nine Full-Length Amyloidogenic κ1 Immunoglobulin Light Chains†

Biochemistry ◽  
2007 ◽  
Vol 46 (49) ◽  
pp. 14259-14271 ◽  
Author(s):  
Lawreen H. Connors ◽  
Yan Jiang ◽  
Marianna Budnik ◽  
Roger Théberge ◽  
Tatiana Prokaeva ◽  
...  
Keyword(s):  
Primary Structure ◽  
Full Length ◽  
Light Chains ◽  
Germline Gene ◽  
Immunoglobulin Light Chains ◽  
Post Translational Modifications ◽  
Gene Usage

scholarly journals Stabilization of amyloidogenic immunoglobulin light chains by small molecules

2019 ◽  
Vol 116 (17) ◽  
pp. 8360-8369 ◽  
Author(s):  
Gareth J. Morgan ◽  
Nicholas L. Yan ◽  
David E. Mortenson ◽  
Enrico Rennella ◽  
Joshua M. Blundon ◽  
...  
Keyword(s):  
Small Molecules ◽  
Light Chain ◽  
Cardiac Involvement ◽  
Plasma Cells ◽  
Full Length ◽  
Light Chains ◽  
Immunoglobulin Light Chains ◽  
X Ray ◽  
Tissue Degeneration ◽  
Dimerization Interface

In Ig light-chain (LC) amyloidosis (AL), the unique antibody LC protein that is secreted by monoclonal plasma cells in each patient misfolds and/or aggregates, a process leading to organ degeneration. As a step toward developing treatments for AL patients with substantial cardiac involvement who have difficulty tolerating existing chemotherapy regimens, we introduce small-molecule kinetic stabilizers of the native dimeric structure of full-length LCs, which can slow or stop the amyloidogenicity cascade at its origin. A protease-coupled fluorescence polarization-based high-throughput screen was employed to identify small molecules that kinetically stabilize LCs. NMR and X-ray crystallographic data demonstrate that at least one structural family of hits bind at the LC–LC dimerization interface within full-length LCs, utilizing variable-domain residues that are highly conserved in most AL patients. Stopping the amyloidogenesis cascade at the beginning is a proven strategy to ameliorate postmitotic tissue degeneration.

scholarly journals Aggregation of Full-length Immunoglobulin Light Chains from Systemic Light Chain Amyloidosis (AL) Patients Is Remodeled by Epigallocatechin-3-gallate

2016 ◽  
Vol 292 (6) ◽  
pp. 2328-2344 ◽  
Author(s):  
Kathrin Andrich ◽  
Ute Hegenbart ◽  
Christoph Kimmich ◽  
Niraja Kedia ◽  
H. Robert Bergen ◽  
...  
Keyword(s):  
Light Chain ◽  
Full Length ◽  
Light Chains ◽  
Immunoglobulin Light Chains ◽  
Light Chain Amyloidosis

scholarly journals The Role of Protein Thermodynamics and Primary Structure in Fibrillogenesis of Variable Domains from Immunoglobulin Light Chains

2019 ◽  
Vol 141 (34) ◽  
pp. 13562-13571 ◽  
Author(s):  
Enrico Rennella ◽  
Gareth J. Morgan ◽  
Nicholas Yan ◽  
Jeffery W. Kelly ◽  
Lewis E. Kay
Keyword(s):  
Primary Structure ◽  
Light Chains ◽  
Immunoglobulin Light Chains ◽  
Protein Thermodynamics ◽  
Variable Domains

scholarly journals Human rheumatoid factor crossidiotypes. I. WA and BLA are heat-labile conformational antigens requiring both heavy and light chains.

1986 ◽  
Vol 164 (5) ◽  
pp. 1809-1814 ◽  
Author(s):  
V Agnello ◽  
J L Barnes
Keyword(s):  
Rheumatoid Factor ◽  
Primary Structure ◽  
Binding Activity ◽  
Light Chains ◽  
Heat Denaturation ◽  
Antigen Binding ◽  
Rheumatoid Factors ◽  
Simple Method ◽  
Heat Labile

Evidence was obtained that both the WA and BLA crossidiotype (XId) groups are conformational antigens requiring both L and H chains and that with heat denaturation the antigens that define the XIds and antigen-binding activity are lost in parallel. In contrast, the primary structure-dependent crossreactive idiotype (CRI), PSL2, which is only weakly detected on native Wa and Bla monoclonal rheumatoid factors (mRFs), became prominently detected on the heated Wa and Bla mRFs. Heat denaturation may provide a simple method for distinguishing Ids determined by conformational antigen from primary structure-dependent Ids. In addition to heat denaturation, some acid conditions commonly used for preparation of RFs were also found to cause marked loss of Id antigen. The finding of PSL2-CRI on Bla mRF indicates that this Id is not unique to the WA XId.

Diversity of expressed V and J regions of immunoglobulin light chains in Xenopus laevis

1993 ◽  
Vol 23 (8) ◽  
pp. 1980-1986 ◽  
Author(s):  
Sue E. Stewart ◽  
Louis Du Pasquier ◽  
Lisa A. Steiner
Keyword(s):  
Xenopus Laevis ◽  
Light Chains ◽  
Immunoglobulin Light Chains
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