Domain Stability in Immunoglobulin Light Chain Deposition Disorders

Abstract

Publisher Summary This chapter begins with a brief introduction to the general problem of protein deposition, with a review of possible molecular mechanisms. Subsequent sections describe results on the analysis of light chain aggregation and deposition in several forms of human disease and in Escherichia coli (E. coli) expression. The chapter reviews some general factors that play roles in the mechanism of amyloid deposition in vivo. Clearly, both physiological and molecular factors are important. The challenge has been and continues to be in defining how the relevant factors together control the timing, tissue location, and medical consequences of amyloid deposition. A major role for mutational effects on domain stability as a determinant of susceptibility to in vivo deposition of light chain V L domains is discussed. The potential importance of domain stability warrants a consideration here of the role of amino acid sequence in V L and light chain folding stability. Site directed mutagenesis and recombinant expression techniques can now be used, however, to make point mutants in the light chain or the V L domain to isolate and test suspected amyloidogenic mutations.