Structural Relationship of λ-Type Light Chains with AL Amyloidosis

Three human amyloidogenic Bence Jones proteins, NIG76 VλII, NIG204 VλI, and NIG250 VλV, were characterized. In a comparative study, three amino acids, Ser-25a, Thr-68, and Val-95, were found to be common to amyloidogenic proteins of the VλII subgroup. NIG204 had an insertion of Pro residue following position 30 (30a). Proteins having an insertion at this position are invariantly amyloidogenic. NIG250 had a characteristic VλVVLdomain, with Mcg+and KERN+CLdomain isotypes. Following the protein DEL, this is the second example of this subgroup. No common residue is found in the other subgroup proteins but unique substitutions do occur. It would seem that any substitution that causes an alteration in the protein conformation may lead to its being more prone to association with the amyloid processes.