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一种人类Ro/SS-A自身抗原的分子克隆、表达及19号染色体定位

Molecular cloning, expression, and chromosome 19 localization of a human Ro/SS-A autoantigen.

作者信息

McCauliffe D P, Lux F A, Lieu T S, Sanz I, Hanke J, Newkirk M M, Bachinski L L, Itoh Y, Siciliano M J, Reichlin M

机构信息

Department of Dermatology, University of Texas, Southwestern Medical Center, Dallas 75238.

出版信息

J Clin Invest. 1990 May;85(5):1379-91. doi: 10.1172/JCI114582.

Abstract

Ro/SS-A antibodies are found in a number of human autoimmune disorders including Sjogren's syndrome and several systemic lupus erythematosus-related disorders. These heterogeneous autoantibodies are known to recognize several distinct cellular antigens. With synthetic oligonucleotides corresponding to amino acid sequence information we have isolated a full-length cDNA clone which encodes a human Ro ribonucleoprotein autoantigen. The 1,890-base pair clone contains an open reading frame that encodes a 417-amino acid, 48-kD polypeptide that migrates aberrantly at 60 kD by SDS-PAGE. Rabbit antibodies raised against this protein's recently described amino-terminal epitope react with a previously identified 52-kD human Ro protein and immunoprecipitate the human cytoplasmic RNAs. Ultraviolet light cross-linking studies suggest that this Ro protein binds each of the four major human cytoplasmic RNAs. The deduced amino acid sequence is 63% homologous to an Onchocerca volvulus antigen. Southern filter hybridization analysis indicates that this gene is not highly polymorphic and exists as a single copy in the human genome. Chromosomal localization studies place this gene on the short arm of chromosome 19 near the gene encoding the low density lipoprotein receptor.

摘要

Ro/SS-A抗体存在于多种人类自身免疫性疾病中,包括干燥综合征和几种与系统性红斑狼疮相关的疾病。已知这些异质性自身抗体可识别几种不同的细胞抗原。利用与氨基酸序列信息对应的合成寡核苷酸,我们分离出了一个全长cDNA克隆,该克隆编码一种人类Ro核糖核蛋白自身抗原。这个1890碱基对的克隆包含一个开放阅读框,编码一个417个氨基酸、48kD的多肽,该多肽在SDS-PAGE中以60kD的异常迁移率迁移。针对该蛋白最近描述的氨基末端表位产生的兔抗体与先前鉴定的52kD人类Ro蛋白发生反应,并免疫沉淀人类细胞质RNA。紫外线交联研究表明,这种Ro蛋白与四种主要的人类细胞质RNA中的每一种都结合。推导的氨基酸序列与盘尾丝虫抗原具有63%的同源性。Southern印迹杂交分析表明,该基因多态性不高,在人类基因组中以单拷贝形式存在。染色体定位研究将该基因定位于19号染色体短臂上,靠近编码低密度脂蛋白受体的基因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a09/296583/aeae78edb57a/jcinvest00071-0045-a.jpg

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