Mutations in specific structural regions of immunoglobulin light chains are associated with free light chain levels in patients with AL amyloidosis.

ABSTRACT:

Background

The amyloidoses are protein misfolding diseases characterized by the deposition of amyloid that leads to cell death and tissue degeneration. In immunoglobulin light chain amyloidosis (AL), each patient has a unique monoclonal immunoglobulin light chain (LC) that forms amyloid deposits. Somatic mutations in AL LCs make these proteins less thermodynamically stable than their non-amyloidogenic counterparts, leading to misfolding and ultimately the formation of amyloid fibrils. We hypothesize that location rather than number of non-conservative mutations determines the amyloidogenicity of light chains.

Methodology/principal findings

We performed sequence alignments on the variable domain of 50 kappa and 91 lambda AL light chains and calculated the number of non-conser

SUBMITTER: Poshusta TL 

PROVIDER: S-EPMC2664898 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature