Thymine and guanine base specificity of human myeloma proteins with anti-DNA activity.
Thymine and guanine base specificity of human myeloma proteins with anti-DNA activity.
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具有抗 DNA 活性的人骨髓瘤蛋白的胸腺嘧啶和鸟嘌呤碱基特异性。
DOI：
10.1172/jci112699
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发表时间：
1986
期刊：
影响因子：
--
通讯作者：
Stollar,BD
中科院分区：
文献类型：
--
作者：
Zouali,M;Stollar,BD
为了进一步了解DNA-自身抗体相互作用的分子基础，我们表征了结合DNA的三种IgG人骨髓瘤蛋白的特异性。我们测量了它们与合成的单链和双链均聚多核苷酸、随机和交替共聚物、寡核苷酸以及与非核酸载体缀合的核苷酸或核苷的结合。所有三种抗体结合单链核酸，包括多核糖核苷酸和多脱氧核糖核苷酸。它们对不同碱基组成的多核苷酸的相对亲和力不同。含有嘌呤鸟嘌呤或次黄嘌呤和/或嘧啶胸腺嘧啶的聚合物与所有三种蛋白质反应最强烈。一种与多聚（G）、多聚（I）或多聚（dT）反应的骨髓瘤蛋白，也与相应的核苷或核苷酸结合，这些核苷或核苷酸与牛血清白蛋白结合。没有抗体与碱基配对的双螺旋多核苷酸（双链RNA、RNA-DNA杂合体或双链DNA）反应。结果表明，碱基特异性在它们的反应中是突出的，并且单链多核苷酸中的可接近表位在双链螺旋中的碱基配对后被掩蔽。这些发现表明了一种模型，其中鸟嘌呤和次黄嘌呤的N1和O 6位置以及胸腺嘧啶的N3和O 4位置与抗体结合位点的氨基酸相互作用。
To further our understanding of the molecular basis of DNA-autoantibody interactions, we have characterized the specificities of three IgG human myeloma proteins that bind DNA. We measured their binding to synthetic single- and double-stranded homopolynucleotides, random and alternating copolymers, oligonucleotides, and nucleotides or nucleosides conjugated to non-nucleic acid carriers. All three antibodies bound single-stranded nucleic acids, including both polyribonucleotides and polydeoxyribonucleotides. They varied in relative affinities for polynucleotides of varying base composition. Polymers containing the purines guanine or hypoxanthine and/or the pyrimidine thymine were most reactive with all three proteins. A myeloma protein that reacted with poly(G), poly(I), or poly(dT) also bound to the corresponding nucleosides or nucleotides conjugated to bovine serum albumin. None of the antibodies reacted with base-paired double-helical polynucleotides (double-stranded RNA, RNA-DNA hybrid or double-stranded DNA). The results indicate that base specificity is prominent in their reactions and that the accessible epitopes in single-stranded polynucleotides become masked upon base pairing in double-stranded helices. These findings suggest a model in which positions N1 and O6 of guanine and hypoxanthine and N3 and O4 of thymine interact with amino acids of the antibody-combining site.