ArticleThe Journal of biological chemistry2018
Identification of two principal amyloid-driving segments in variable domains of Ig light chains in systemic light-chain amyloidosis.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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Who cites it
19 citing papers in PubMed, 53 citations in OpenAlex.
- Cryo-EM structures of light chain fibrils from abdominal fat biopsies of multiple myeloma patients.Nature communications · 2026Article
- IgStrand: A universal residue numbering scheme for the immunoglobulin-fold (Ig-fold) to study Ig-proteomes and Ig-interactomes.PLoS computational biology · 2025Review
- Ig or Not Ig? That Is the Question: The Nucleating Supersecondary Structure of the Ig-Fold and the Extended Ig Universe.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Cellular stress and coagulation factor production: when more is not necessarily better.Journal of thrombosis and haemostasis : JTH · 2023Review
- 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
- Widespread amyloidogenicity potential of multiple myeloma patient-derived immunoglobulin light chains.BMC biology · 2023Article
- Bioinformatic identification of previously unrecognized amyloidogenic proteins.The Journal of biological chemistry · 2022Article
- Protease-sensitive regions in amyloid light chains: what a common pattern of fragmentation across organs suggests about aggregation.The FEBS journal · 2022Article
- Understanding AL amyloidosis with a little help fromFrontiers in immunology · 2022Review
- A Conservative Point Mutation in a Dynamic Antigen-binding Loop of Human Immunoglobulin λ6 Light Chain Promotes Pathologic Amyloid Formation.Journal of molecular biology · 2021Article
- Mass spectrometry characterization of light chain fragmentation sites in cardiac AL amyloidosis: insights into the timing of proteolysis.The Journal of biological chemistry · 2020Article
- Atomistic fibrillar architectures of polar prion-inspired heptapeptides.Chemical science · 2020Article
- Understanding Mesangial Pathobiology in AL-Amyloidosis and Monoclonal Ig Light Chain Deposition Disease.Kidney international reports · 2020Review
- Article
- Fatal amyloid formation in a patient's antibody light chain is caused by a single point mutation.eLife · 2020Article
- Article
- The Role of Protein Thermodynamics and Primary Structure in Fibrillogenesis of Variable Domains from Immunoglobulin Light Chains.Journal of the American Chemical Society · 2019Article
- Cryo-EM structure of a light chain-derived amyloid fibril from a patient with systemic AL amyloidosis.Nature communications · 2019Article
- Molecular mechanism of amyloidogenic mutations in hypervariable regions of antibody light chains.The Journal of biological chemistryArticle
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Systemic light-chain amyloidosis (AL) is a human disease caused by overexpression of monoclonal immunoglobulin light chains that form pathogenic amyloid fibrils. These amyloid fibrils deposit in tissues and cause organ failure. Proteins form amyloid fibrils when they partly or fully unfold and expose segments capable of stacking into β-sheets that pair and thereby form a tight, dehydrated interface. These structures, termed steric zippers, constitute the spines of amyloid fibrils. Here, using a combination of computational (with ZipperDB and Boston University ALBase), mutational, biochemical, and protein structural analyses, we identified segments within the variable domains of Ig light chains that drive the assembly of amyloid fibrils in AL. We demonstrate that there are at least two such segments and that each one can drive amyloid fibril assembly independently of the other. Our analysis revealed that peptides derived from these segments form steric zippers featuring a typical dry interface with high-surface complementarity and occupy the same spatial location of the Greek-key immunoglobulin fold in both λ and κ variable domains. Of note, some predicted steric-zipper segments did not form amyloid fibrils or assembled into fibrils only when removed from the whole protein. We conclude that steric-zipper propensity must be experimentally validated and that the two segments identified here may represent therapeutic targets. In addition to elucidating the molecular pathogenesis of AL, these findings also provide an experimental approach for identifying segments that drive fibril formation in other amyloid diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.