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

Vittorio Bellotti, Monica Stoppini, Palma P. Mangione, Alessandro Fornasieri, Li Min, Giampaolo Merlini, Giuseppina Ferri

Research output: Contribution to journalArticlepeer-review

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 125I labelled light chain into mice. No deposition was detectable in the case of INC and MOS.

Original languageEnglish
Pages (from-to)161-167
Number of pages7
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1317
Issue number3
DOIs
Publication statusPublished - Dec 16 1996

Keywords

  • Amyloidosis
  • Light chain
  • Light chain deposition disease
  • Unfolding

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Biophysics

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