De Novo Sequencing and Characterization of Post-translational Modifications of an Amyloidogenic Immunoglobulin Kappa Light Chain

摘要

It has been shown that reduced folding stability is a unifying property of amyloidogenic immunoglobulin light chains. Amino acid replacements in the variable region and certain post-translational modifications (PTMs) can destabilize the folding state of the light chains and enable them to populate a partially unfolded intermediate state which may play a key role in fibril formation and organ damage. A mass spectrometry (MS) based method was employed to investigate amyloidogenic light chains from patients diagnosed with AL amyloidosis for detection of sequence variations and PTMs. In this study, the primary structure of a kappa III light chain (01-140) variable region was characterized de novo using tandem MS before genetic material and the cDNA sequence were obtained