Glycosaminoglycans promote fibril formation by amyloidogenic immunoglobulin light chains through a transient interaction.

ABSTRACT: Amyloid formation occurs when a precursor protein misfolds and aggregates, forming a fibril nucleus that serves as a template for fibril growth. Glycosaminoglycans are highly charged polymers known to associate with tissue amyloid deposits that have been shown to accelerate amyloidogenesis in vitro. We studied two immunoglobulin light chain variable domains from light chain amyloidosis patients with 90% sequence identity, analyzing their fibril formation kinetics and binding properties with different glycosaminoglycan molecules. We find that the less amyloidogenic of the proteins shows a weak dependence on glycosaminoglycan size and charge, while the more amyloidogenic protein responds only minimally to changes in the glycosaminoglycan. These glycosaminoglycan effects on fibril formation d

SUBMITTER: Martin DJ 

PROVIDER: S-EPMC3133826 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature