Site-Specific Interactions with Copper Promote Amyloid Fibril Formation for λ6aJL2-R24G.

ABSTRACT: Light-chain amyloidosis (AL) is one of the most common systemic amyloidoses, and it is characterized by the deposition of immunoglobulin light chain (LC) variable domains as insoluble amyloid fibers in vital organs and tissues. The recombinant protein 6aJL2-R24G contains λ6a and JL2 germline genes and also contains the Arg24 by Gly substitution. This mutation is present in 25% of all amyloid-associated λ6 LC cases, reduces protein stability, and increases the propensity to form amyloid fibers. In this study, it was found that the interaction of 6aJL2-R24G with Cu(II) decreases the thermal stability of the protein and accelerates the amyloid fibril formation, as observed by fluorescence spectroscopy. Isothermal calorimetry titration showed that Cu(II) binds to the protein with micromolar af

SUBMITTER: Pelaez-Aguilar AE 

PROVIDER: S-EPMC7143407 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature