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与多肌炎-硬皮病重叠综合征相关的核仁100-kD蛋白编码cDNA的克隆与特性分析

Cloning and characterization of the cDNA coding for a polymyositis-scleroderma overlap syndrome-related nucleolar 100-kD protein.

作者信息

Blüthner M, Bautz F A

机构信息

Institute of Molecular Genetics, University of Heidelberg, Germany.

出版信息

J Exp Med. 1992 Oct 1;176(4):973-80. doi: 10.1084/jem.176.4.973.

Abstract

About 50% of patients with the polymyositis-scleroderma overlap syndrome are reported to have autoantibodies to a nucleolar particle termed PM/Scl. The particle consists of several polypeptides of which two proteins of 75 and 100 kD have been identified as the major antigenic components. Here we report on the cDNA cloning and partial epitope mapping of the 100-kD autoantigen from human placenta and HeLa lambda gt11 libraries. The deduced amino acid sequence encodes a protein of 885 amino acid residues with a molecular mass of 100.8 kD. Rabbit antibodies raised against a recombinant protein fragment reacted in immunofluorescence and immunoblotting in the same manner as human autoantibodies directed against the nucleolar 100-kD protein. Sequence analysis shows close homology to a consensus sequence of 12 amino acids from serine/threonine kinases, suggesting a possible function for this autoantigen. A major antigenic region is found to be located within the NH2-terminal third of the polypeptide.

摘要

据报道,约50%的多发性肌炎-硬皮病重叠综合征患者体内存在针对一种名为PM/Scl的核仁颗粒的自身抗体。该颗粒由几种多肽组成,其中已鉴定出两种分子量分别为75kD和100kD的蛋白质为主要抗原成分。在此,我们报告从人胎盘和HeLa λgt11文库中对100kD自身抗原进行cDNA克隆和部分表位定位的研究。推导的氨基酸序列编码一个由885个氨基酸残基组成的蛋白质,分子量为100.8kD。针对重组蛋白片段产生的兔抗体在免疫荧光和免疫印迹中的反应方式与针对核仁100kD蛋白的人自身抗体相同。序列分析显示与丝氨酸/苏氨酸激酶的12个氨基酸共有序列具有高度同源性,提示该自身抗原可能具有某种功能。发现一个主要抗原区域位于多肽的氨基末端三分之一范围内。

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