Issue 76, 2018

Immunoglobulin light chain amyloid aggregation

Abstract

Light chain (AL) amyloidosis is a devastating, complex, and incurable protein misfolding disease. It is characterized by an abnormal proliferation of plasma cells (fully differentiated B cells) producing an excess of monoclonal immunoglobulin light chains that are secreted into circulation, where the light chains misfold, aggregate as amyloid fibrils in target organs, and cause organ dysfunction, organ failure, and death. In this article, we will review the factors that contribute to AL amyloidosis complexity, the findings by our laboratory from the last 16 years and the work from other laboratories on understanding the structural, kinetics, and thermodynamic contributions that drive immunoglobulin light chain-associated amyloidosis. We will discuss the role of cofactors and the mechanism of cellular damage. Last, we will review our recent findings on the high resolution structure of AL amyloid fibrils. AL amyloidosis is the best example of protein sequence diversity in misfolding diseases, as each patient has a unique combination of germline donor sequences and multiple amino acid mutations in the protein that forms the amyloid fibril.

Graphical abstract: Immunoglobulin light chain amyloid aggregation

Article information

Article type
Feature Article
Submitted
01 Jun 2018
Accepted
01 Aug 2018
First published
01 Aug 2018

Chem. Commun., 2018,54, 10664-10674

Immunoglobulin light chain amyloid aggregation

L. M. Blancas-Mejia, P. Misra, C. J. Dick, S. A. Cooper, K. R. Redhage, M. R. Bergman, T. L. Jordan, K. Maar and M. Ramirez-Alvarado, Chem. Commun., 2018, 54, 10664 DOI: 10.1039/C8CC04396E

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