Complementary DNA sequence of human amyloidogenic immunoglobulin light-chain precursors.

Pierre Aucouturier 1, * Ahmed Khamlichi 1 Jean-Louis Preud'homme 1 Marc Bauwens 2 Guy Touchard 2 Michel Cogné 1
* Corresponding author
1 CNRS URA 1172 - Laboratoire d'Immunologie et Immunopathologie [CHU Poitiers]
2 Département de Néphrologie [CHU Poitiers]
Abstract : The primary structure of three amyloid precursor light chains was deduced from the sequence of complementary DNA (cDNA) from bone marrow cells from patients affected with classical lambda (patient Air) or kappa (patient Arn) amyloidosis and from a patient (Aub) in whom lambda amyloid deposits were unusual by their perimembranous location in the kidney glomerulus. All three RNAs were of normal size, as estimated by Northern blotting, and encoded normal-sized light chains. The deduced light-chain sequence from patient Arn was related to the V kappa 1 subgroup, and included ten residues that had not been previously reported at these positions, only one of which (Leu-21) was located in a beta-sheet (4-2). The unusual presence of Asn-70 determined a potential N-glycosylation site. The sequence of the light chain from patient Air belonged to the V lambda 1 subgroup, and included three unusually located amino acid residues, one of which had already been reported in an amyloidogenic lambda-chain. The sequence of the light chain from patient Aub was related to the V lambda 3 subgroup, and contained five amino acid residues that had not previously been described at the corresponding positions; two of them (His-36 and Ser-77) were located in beta-sheets (3-1 and 4-3 respectively). This sequence was also peculiar because of the presence of numerous acidic residues in the complementarity-determining regions. Such unusual primary structures might be responsible for the amyloidogenic properties of these light-chain precursors.
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Pierre Aucouturier, Ahmed Khamlichi, Jean-Louis Preud'homme, Marc Bauwens, Guy Touchard, et al.. Complementary DNA sequence of human amyloidogenic immunoglobulin light-chain precursors.. Biochemical Journal, Portland Press, 1992, 285, pp.149-52. ⟨10.1042/bj2850149⟩. ⟨inserm-01876794⟩

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