The Kinetic Stability of a Full-Length Antibody Light Chain Dimer Determines whether Endoproteolysis Can Release Amyloidogenic Variable Domains.

ABSTRACT: Light chain (LC) amyloidosis (AL amyloidosis) appears to be caused by the misfolding, or misfolding and aggregation of an antibody LC or fragment thereof and is fatal if untreated. LCs are secreted from clonally expanded plasma cells, generally as disulfide-linked dimers, with each monomer comprising one constant and one variable domain. The energetic contribution of each domain and the role of endoproteolysis in AL amyloidosis remain unclear. To investigate why only some LCs form amyloid and cause organ toxicity, we measured the aggregation propensity and kinetic stability of LC dimers and their associated variable domains from AL amyloidosis patients and non-patients. All the variable domains studied readily form amyloid fibrils, whereas none of the full-length LC dimers, even those from

SUBMITTER: Morgan GJ 

PROVIDER: S-EPMC5065776 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature