STRUCTURAL AND FUNCTIONAL-CHARACTERIZATION OF 3 HUMAN-IMMUNOGLOBULIN KAPPA-LIGHT-CHAINS WITH DIFFERENT PATHOLOGICAL IMPLICATIONS

The structural properties of three immunoglobulins light chains: kappa SCI, responsible for light chain deposition disease (Bellotti, V., St oppini, M., Merlini, G., Zapponi, M.C., Meloni, M.L., Banfi, G. and Fe rri, G. (1991) Biochim. Biophys. Acta 1097, 177-182), k INC responsibl e for light chain amyloidosis (Ferri, G., Stoppini, M., Iadarola, P., Bellotti, V. and Merlini, G. (1989) Biochim. Biophys, Acta 995, 103-10 8) and the non-pathogenic kappa MOS were analyzed by fluorescence spec troscopy and circular dichroism. Comparative evaluation of the data sh ows that SCI and MOS have similar stability under different conditions , while the amyloid k INC behaves as a very unstable protein. As calcu lated from the GdnHCl curves, the midpoint of unfolding transition was 1.35 M for SCI, 1.20 M for MOS and 0.1 M for INC, Analysis of CD spec tra evidences that the three proteins conserve their conformation in t he range of pH 4-8. Change in temperature at pH 4.0 produces the prema ture transition of INC (T-m 40 degrees C) with respect to SCI and MOS (T-m 50 degrees C). At this pH both the pathological SCI and INC light chains aggregate at a temperature of 20 degrees C lower than the norm al counterpart. The specific kidney deposition of kappa SCI has been e videnced after injection of the I-125 labelled light chain into mice. No deposition was detectable in the case of INC and MOS.