ArticleJournal of molecular biology2021
A Conservative Point Mutation in a Dynamic Antigen-binding Loop of Human Immunoglobulin λ6 Light Chain Promotes Pathologic Amyloid Formation.
Article in Journal of molecular biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 21 citations in OpenAlex.
- Small Molecule Stabilization of Diverse Amyloidogenic Immunoglobulin Light Chains Revealed by Hydrogen-Deuterium Exchange Mass Spectrometry.Journal of molecular biology · 2026Article
- Multiple Myeloma Concomitant with AL Amyloidosis: Histopathological Aspects of the Common Plasma Cell Spectrum.International journal of molecular sciences · 2026Article
- Cryo-EM of Cardiac AL-224L Amyloid Reveals Shared Structural Motifs and Mutation-induced Differences in λ6 Light Chain Fibrils.Journal of molecular biology · 2026Article
- Small molecule stabilization of diverse amyloidogenic immunoglobulin light chains revealed by hydrogen-deuterium exchange mass spectrometry.bioRxiv : the preprint server for biology · 2026Article
- Article
- Clone-specific residue changes at multiple positions are associated with amyloid formation by antibody light chains.Frontiers in immunology · 2025Article
- Conformational Differences in the Light Chain Constant Domain of Immunoglobulin G and Free Light Chain May Influence Proteolysis in AL Amyloidosis.Journal of molecular biology · 2024Article
- Role of complementarity-determining regions 1 and 3 in pathologic amyloid formation by human immunoglobulin κ1 light chains.Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis · 2023Article
- Role of the mechanisms for antibody repertoire diversification in monoclonal light chain deposition disorders: when a friend becomes foe.Frontiers in immunology · 2023Review
- Simple and Fast Maximally Deuterated Control (maxD) Preparation for Hydrogen-Deuterium Exchange Mass Spectrometry Experiments.Analytical chemistry · 2022Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Immunoglobulin light chain (LC) amyloidosis (AL) is a life-threatening human disease wherein free mono-clonal LCs deposit in vital organs. To determine what makes some LCs amyloidogenic, we explored patient-based amyloidogenic and non-amyloidogenic recombinant LCs from the λ6 subtype prevalent in AL. Hydrogen-deuterium exchange mass spectrometry, structural stability, proteolysis, and amyloid growth studies revealed that the antigen-binding CDR1 loop is the least protected part in the variable domain of λ6 LC, particularly in the AL variant. N32T substitution in CRD1 is identified as a driver of amyloid formation. Substitution N32T increased the amyloidogenic propensity of CDR1 loop, decreased its protection in the native structure, and accelerated amyloid growth in the context of other AL substitutions. The destabilizing effects of N32T propagated across the molecule increasing its dynamics in regions ∼30 Å away from the substitution site. Such striking long-range effects of a conservative point substitution in a dynamic surface loop may be relevant to Ig function. Comparison of patient-derived and engineered proteins showed that N32T interactions with other substitution sites must contribute to amyloidosis. The results suggest that CDR1 is critical in amyloid formation by other λ6 LCs.
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