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Structure and function of a novel human lectin P35

新型人类凝集素P35的结构和功能

基本信息

批准号：
06670360
负责人：
ENDO Yuichi
金额：
$ 1.41万
依托单位：
Fukushima Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

项目摘要

Collectins are C-type lectins with collagenous and carbohydrate recognition domains and are involved in the first line host defense against pathogens. We report here a novel Ca^<2+>-dependent and ClcNAc-binding lectin consisting of subunit of 35 kDa (P35) with a collagenlike sequence. It forms a homopolymer by means of intermolecular disulfide bondingas is the case with collectins, P35 cDNA was cloned from a human liver cDNA library, and the deduced amino acid sequence of 313 residues revealed that the mature form of p35 consists mainly of collagen-and fibrinogen-like domains. The latter contained two protential Ca^<2+>-binding sites that may be involved in carbohydrate binding. The overall sequence of P35 was highly homologous to porcine ficolins alpha and beta. P35 enhanced phagocytosis of Salmonella typhimurium by neutrophils, suggesting an opsonic effect via the collagen region. Therefore, P35 represents a new type of GlcNAc-binding lectin with structural and functional similarities to collectins involved in innate immunity.We isolated genomic clones of the P35 gene and found that P35 is encoded by eight exons. In addition, we isolated another distinct genomic clone corresponding to the upstream region of a P35-related gene which has an exon organization closely resembling that of the P35 gene. Northern blotting revealed that the P35 gene is expressed mainly in liver, whereas the P35-related gene is expressed in lung and peripheral blood leukocytes, demonstrating tissue-specific expression of these two genes. Both genes were assigned to a closely related region of chromosome 9 at 9934. Further studies are needed to elucidate the function of the P35-related gene product, and to establish the structural and functional relationship with P35.

凝集素是具有胶原和碳水化合物识别结构域的C-型凝集素，并且参与抵抗病原体的第一线宿主防御。我们在此报道了一种新的钙离子依赖性和ClcNAc结合性凝集素，它由35 kDa亚基（P35）和胶原样序列组成。从人肝cDNA文库中克隆了P35的cDNA，经313个氨基酸的序列分析表明，成熟的P35蛋白主要由胶原样结构域和纤维蛋白原样结构域组成。后者含有两个潜在的Ca^2+结合位点，可能与碳水化合物结合有关。P35的整体序列与猪纤维胶凝蛋白α和β高度同源。P35增强嗜中性粒细胞对鼠伤寒沙门氏菌的吞噬作用，表明通过胶原区域的调理作用。因此，P35代表了一种新型的GlcNAc结合凝集素，其结构和功能与参与先天免疫的collectins相似。此外，我们分离出另一个不同的基因组克隆对应的上游区域的P35相关基因，其具有一个外显子组织密切类似的P35基因。北方杂交结果显示，P35基因主要在肝脏表达，而P35相关基因在肺和外周血白细胞中表达，表明这两个基因具有组织特异性表达。这两个基因被分配到9号染色体9934处的密切相关区域。P35相关基因产物的功能及与P35的结构和功能关系有待进一步研究。