Identification of two principal amyloid-driving segments in variable domains of Ig light chains in systemic light-chain amyloidosis.

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

SUBMITTER: Brumshtein B 

PROVIDER: S-EPMC6314132 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature