The Orthologue of Sjogren's Syndrome Nuclear Autoantigen 1 (SSNA1) in Trypanosoma brucei Is an Immunogenic Self-Assembling Molecule
The Orthologue of Sjogren's Syndrome Nuclear Autoantigen 1 (SSNA1) in Trypanosoma brucei Is an Immunogenic Self-Assembling Molecule
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DOI：
10.1371/journal.pone.0031842
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发表时间：
2012-02-20
期刊：
影响因子：
3.7
通讯作者：
Smith, Deborah F.
中科院分区：
文献类型：
--
作者：
Price, Helen P.;Hodgkinson, Michael R.;Smith, Deborah F.
原发性干燥综合征（PSS）是一种高度流行的自身免疫性疾病，通常表现为外分泌腺的淋巴细胞浸润，导致泪腺和唾液分泌慢性受损。干燥综合征核自身抗原1（SSNA 1或NA 14）是PSS中自身抗体的主要特异性靶点，但这种蛋白质的确切功能和临床相关性在很大程度上是未知的。该基因的直系同源物在许多常用的模式生物中不存在，但存在于莱茵衣藻（Chlamyopyrinhardtii）（其中被称为DIP 13）和大多数原生动物中。我们报告的功能特性的直向同源物SSNA 1的动质体寄生虫，布氏锥虫。TbDIP 13和人SSNA 1都是小卷曲螺旋蛋白，预测它们是肌动蛋白结合蛋白原肌球蛋白的远程同源物。我们使用比较蛋白质组学方法来确定TbDIP 13的潜在相互作用伙伴。我们还表明TbDIP 13能够在体外和体内自组装成纤维样结构，这可能有助于其免疫原性。内源性TbDIP 13部分共定位与乙酰化α-微管蛋白在昆虫procyclic阶段的寄生虫。然而，在培养的血流和T.布氏杆菌对寄生虫的生长或形态几乎没有影响，这表明在寄生虫生命周期的另一个阶段存在一定程度的功能冗余或功能。
Primary Sjogren's Syndrome (PSS) is a highly prevalent autoimmune disease, typically manifesting as lymphocytic infiltration of the exocrine glands leading to chronically impaired lacrimal and salivary secretion. Sjogren's Syndrome nuclear autoantigen 1 (SSNA1 or NA14) is a major specific target for autoantibodies in PSS but the precise function and clinical relevance of this protein are largely unknown. Orthologues of the gene are absent from many of the commonly used model organisms but are present in Chlamyodomonas reinhardtii (in which it has been termed DIP13) and most protozoa. We report the functional characterisation of the orthologue of SSNA1 in the kinetoplastid parasite, Trypanosoma brucei. Both TbDIP13 and human SSNA1 are small coiled-coil proteins which are predicted to be remote homologues of the actin-binding protein tropomyosin. We use comparative proteomic methods to identify potential interacting partners of TbDIP13. We also show evidence that TbDIP13 is able to self-assemble into fibril-like structures both in vitro and in vivo, a property which may contribute to its immunogenicity. Endogenous TbDIP13 partially co-localises with acetylated alpha-tubulin in the insect procyclic stage of the parasite. However, deletion of the DIP13 gene in cultured bloodstream and procyclic stages of T. brucei has little effect on parasite growth or morphology, indicating either a degree of functional redundancy or a function in an alternative stage of the parasite life cycle.