Mechanistic Insights into the Early Events in the Aggregation of Immunoglobulin Light Chains.

ABSTRACT: Little is known about the mechanism of amyloid assembly in immunoglobulin light chain (AL) amyloidosis, in contrast to other amyloid diseases. Early events in the aggregation pathway are especially important, as these soluble species could be cytotoxic intermediates playing a critical role in the initiation of the amyloid assembly. In this work, we discuss the mechanism of the early events in in vitro fibril formation of immunoglobulin light chain AL-09 and AL-12 (involved in cardiac amyloidosis) and its germline (control) protein κI O18/O8. Previous work from our laboratory showed that AL-12 adopts a canonical dimer conformation (like the germline protein), whereas AL-09 presents an altered dimer interface as a result of somatic mutations. Both AL-12 and AL-09 aggregate with similar rates

SUBMITTER: Misra P 

PROVIDER: S-EPMC6650354 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature