Aucouturier P, Khamlichi A A, Preud'homme J L, Bauwens M, Touchard G, Cogné M
Laboratory of Immunology, CNRS URA 1172, Poitiers, France.
Biochem J. 1992 Jul 1;285 ( Pt 1)(Pt 1):149-52. doi: 10.1042/bj2850149.
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.
通过对患有典型λ型（患者Air）或κ型（患者Arn）淀粉样变性的患者以及一名患者（Aub）骨髓细胞的互补DNA（cDNA）序列进行推导，得出了三种淀粉样前体轻链的一级结构。在患者Aub中，λ淀粉样沉积物在肾小球的膜周位置异常。通过Northern印迹法估计，所有三种RNA大小正常，编码的轻链大小也正常。患者Arn推导的轻链序列与Vκ1亚组相关，包括10个此前在这些位置未报道过的残基，其中只有一个（Leu-21）位于β折叠（4-2）中。Asn-70的异常存在确定了一个潜在的N-糖基化位点。患者Air轻链的序列属于Vλ1亚组，包括三个位置异常的氨基酸残基，其中一个已在一条淀粉样生成的λ链中报道过。患者Aub轻链的序列与Vλ3亚组相关，包含五个此前在相应位置未被描述过的氨基酸残基；其中两个（His-36和Ser-77）分别位于β折叠（3-1和4-3）中。该序列也很特殊，因为在互补决定区存在大量酸性残基。这些异常的一级结构可能是这些轻链前体具有淀粉样生成特性的原因。
