Amyloid Proteins: The Amino-Terminal Variable Fragment of Immunoglobulins

Abstract

Abstract Purification of the major protein component of amyloid fibrils from human tissues and from tissues of the experimental murine disease has been accomplished by sequential gel filtration on Sepharose 4 B and Sephadex G-100 columns using 5 M guanidine-HCl in 1 N acetic acid with removal of over 28% of minor constituents. All amyloid proteins have a constant tryptophan content, a high dicarboxylic and short chain amino acid composition, an unreactive or Asx N-terminal group, monomeric molecular weight ranges of from 5000 to 18,300 and, in the human, heterogeneity of amyloid protein between individuals and homogeneity within the individual. Antibodies directed against the major amyloid protein of an individual cross-react with a component in the patient's serum. Immunologic evidence reveals the experimental murine protein to be derived from the N-terminal fragment of an immunoglobulin light chain of λ type and sequence analysis of a human protein categorizes it as derived from the N-terminal variable fragment of a κ I light chain.