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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.

SUBMITTER: Brumshtein B

PROVIDER: S-EPMC4758944 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Inhibition by small-molecule ligands of formation of amyloid fibrils of an immunoglobulin light chain variable domain.

Brumshtein Boris B Esswein Shannon R SR Salwinski Lukasz L Phillips Martin L ML Ly Alan T AT Cascio Duilio D Sawaya Michael R MR Eisenberg David S DS

eLife 20151118

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 dom ...[more]

PMID: 26576950

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