Tertiary structure of human γ6 light chains

AL amyloidosis is a disease process characterized by the pathologic deposition of monoclonal light chains in tissue. To date, only limited information has been obtained on the molecular features that render such light chains amyloidogenic. Although protein products of the major human VK and Vλgene families have been identified in AL deposits, one particular subgroup-λ6 - has been found to be preferentially associated with this disease. Notably, the variable region of λ6 proteins (V λ6) has distinctive primary structural features including the presence in the third framework region (FR3) of two additional amino acid residues that distinguish members of this subgroup from other types of light chains. However, the structural consequences of these alterations have not been elucidated. To determine if λ6 proteins possess unique tertiary structural features, as compared to light chains of other Vλ subgroups, we have obtained x-ray diffraction data on crystals prepared from two recombinant Vλ6 molecules. These c...