Role of domain interactions in the aggregation of full-length immunoglobulin light chains.

ABSTRACT: Amyloid light-chain (LC) amyloidosis is a protein misfolding disease in which the aggregation of an overexpressed antibody LC from a clonal plasma cell leads to organ toxicity and patient death if left untreated. While the overall dimeric architecture of LC molecules is established, with each LC composed of variable (V_L) and constant (C_L) domains, the relative contributions of LC domain-domain interfaces and intrinsic domain stabilities to protection against LC aggregation are not well understood. To address these topics we have engineered a number of domain-destabilized LC mutants and used solution NMR spectroscopy to characterize their structural properties and intrinsic stabilities. Moreover, we used fluorescence spectroscopy to assay their aggregation propensities

SUBMITTER: Rennella E 

PROVIDER: S-EPMC6338840 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature