Inhibition by small-molecule ligands of formation of amyloid fibrils of an immunoglobulin light chain variable domain
Abstract
Overproduction of immunoglobulin light chains leads to systemic amyloidosis, a lethal disease characterized by the formation of amyloid fibrils in patients' tissues. Excess light chains are in equilibrium between dimers and less stable monomers which can undergo irreversible aggregation to the amyloid state. The dimers therefore must disassociate into monomers prior to forming amyloid fibrils. Here we identify ligands that inhibit amyloid formation by stabilizing the Mcg light chain variable domain dimer and shifting the equilibrium away from the amyloid-prone monomer.
- Authors:
-
[1];
- UCLA, Los Angeles, CA (United States); UCLA-DOE Inst. for Genomics and Proteomics, Los Angeles, CA (United States)
- UCLA-DOE Inst. for Genomics and Proteomics, Los Angeles, CA (United States); UCLA, Los Angeles, CA (United States)
- Publication Date:
- Research Org.:
- Argonne National Laboratory (ANL), Argonne, IL (United States)
- Sponsoring Org.:
- National Inst. of Health; National Inst. of General Medical Sciences
- OSTI Identifier:
- 1238288
- Grant/Contract Number:
- AG048120; R25GM055052
- Resource Type:
- Accepted Manuscript
- Journal Name:
- eLife
- Additional Journal Information:
- Journal Volume: 4; Journal Issue: 11, 2015; Journal ID: ISSN 2050-084X
- Publisher:
- eLife Sciences Publications, Ltd.
- Country of Publication:
- United States
- Language:
- ENGLISH
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
Brumshtein, Boris, Esswein, Shannon R., Salwinski, Lukasz, Phillips, Martin L., Ly, Alan T., Cascio, Duilio, Sawaya, Michael R., and Eisenberg, David S. Inhibition by small-molecule ligands of formation of amyloid fibrils of an immunoglobulin light chain variable domain. United States: N. p., 2015.
Web. doi:10.7554/eLife.10935.
Brumshtein, Boris, Esswein, Shannon R., Salwinski, Lukasz, Phillips, Martin L., Ly, Alan T., Cascio, Duilio, Sawaya, Michael R., & Eisenberg, David S. Inhibition by small-molecule ligands of formation of amyloid fibrils of an immunoglobulin light chain variable domain. United States. https://doi.org/10.7554/eLife.10935
Brumshtein, Boris, Esswein, Shannon R., Salwinski, Lukasz, Phillips, Martin L., Ly, Alan T., Cascio, Duilio, Sawaya, Michael R., and Eisenberg, David S. Wed .
"Inhibition by small-molecule ligands of formation of amyloid fibrils of an immunoglobulin light chain variable domain". United States. https://doi.org/10.7554/eLife.10935. https://www.osti.gov/servlets/purl/1238288.
@article{osti_1238288,
title = {Inhibition by small-molecule ligands of formation of amyloid fibrils of an immunoglobulin light chain variable domain},
author = {Brumshtein, Boris and Esswein, Shannon R. and Salwinski, Lukasz and Phillips, Martin L. and Ly, Alan T. and Cascio, Duilio and Sawaya, Michael R. and Eisenberg, David S.},
abstractNote = {Overproduction of immunoglobulin light chains leads to systemic amyloidosis, a lethal disease characterized by the formation of amyloid fibrils in patients' tissues. Excess light chains are in equilibrium between dimers and less stable monomers which can undergo irreversible aggregation to the amyloid state. The dimers therefore must disassociate into monomers prior to forming amyloid fibrils. Here we identify ligands that inhibit amyloid formation by stabilizing the Mcg light chain variable domain dimer and shifting the equilibrium away from the amyloid-prone monomer.},
doi = {10.7554/eLife.10935},
journal = {eLife},
number = 11, 2015,
volume = 4,
place = {United States},
year = {Wed Nov 18 00:00:00 EST 2015},
month = {Wed Nov 18 00:00:00 EST 2015}
}
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Works referencing / citing this record:
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