Structural and functional characterization of three human immunoglobulin κ light chains with different pathological implications

Abstract The structural properties of three immunoglobulins light chains: κ SCI, responsible for light chain deposition disease (Bellotti, V., Stoppini, M., Merlini, G., Zapponi, M.C., Meloni, M.L., Banfi, G. and Ferri, G. (1991) Biochim. Biophys. Acta 1097, 177–182), k INC responsible for light chain amyloidosis (Ferri, G., Stoppini, M., Iadarola, P., Bellotti, V. and Merlini, G. (1989) Biochim. Biophys. Acta 995, 103–108) and the non-pathogenic κ MOS were analyzed by fluorescence spectroscopy and circular dichroism. Comparative evaluation of the data shows that SCI and MOS have similar stability under different conditions, while the amyloid k INC behaves as a very unstable protein. As calculated 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 spectra evidences that the three proteins conserve their conformation in the range of pH 4–8. Change in temperature at pH 4.0 produces the premature transition of INC ( T m 40°C) with respect to SCI and MOS ( T m 50°C). At this pH both the pathological SCI and INC light chains aggregate at a temperature of 20°C lower than the normal counterpart. The specific kidney deposition of κ SCI has been evidenced after injection of the 125 I labelled light chain into mice. No deposition was detectable in the case of INC and MOS.