It has been observed that monoclonal immunoglobulin proteins of the λ VI subgroup have a high propensity to form amyloid deposits. To ascertain whether λ VI proteins have unique structure determinants that would account for self association and resultant fibril formation, we have determined the complete amino acid sequence of the AL amyloid protein WLT. This protein, isolated from the spleen of a patient with AL amyloid, has 134 amino acid residues and contains the entire variable region, the joining segment, and the first tryptic peptide of the constant region. Comparison of the structure of this protein with the 3 completely sequenced λ VI proteins reveals that they are highly homologous and contain a 2-residue insertion at position 68 and 69. Phylogenetic comparisons of the variable domain of all λ VI proteins reveal that the 3 amyloid proteins WLT, SUT, and AR are all more closely related to each other than to the myeloma protein NIG48. Separating the variable domains into framework (FR) and complementarity-determining regions (CD) and recalculating the phylogenetic comparisons, we identify major substitutions in the FR regions of NIG48 in relation to the amyloid proteins. This supports the hypothesis that the formation of AL amyloid is a result of the secondary structure of the FR regions of the precursor molecules.
|Original language||English (US)|
|Number of pages||8|
|Journal||Scandinavian Journal of Immunology|
|State||Published - Dec 1985|
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