Structural relationship of lambda-type light chains with AL amyloidosis

Three human amyloidogenic Pence Jones proteins, NIG76 V lambda II, NIG204 V lambda I, and NIG250 V lambda V, were characterized. In a comparative stud y, three amino acids, Ser-25a, Thr-68, and Val-95, were found to be common to amyloidogenic proteins of the V lambda II subgroup. NIG204 had an insert ion of Pro residue following position 30 (30a). Proteins having an insertio n at this position are invariantly amyloidogenic. NIG250 had a characterist ic V lambda V V-L domain, with Mcg(+) and KERN+ C-L domain isotypes. Follow ing the protein DEL, this is the second example of this subgroup. No common residue is found in the other subgroup proteins but unique substitutions d o occur. It would seem that any substitution that causes an alteration in t he protein conformation may lead to its being more prone to association wit h the amyloid processes. (C) 1999 Academic Press.