The immunoglobulin J chain is an evolutionarily co-opted chemokine.

The immunoglobulin J chain is an evolutionarily co-opted chemokine.
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DOI:
10.1073/pnas.2318995121
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发表时间:
2024-01-16
影响因子:
11.1
通讯作者:
--
中科院分区:
综合性期刊1区
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--
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连接(J)链调节多聚体免疫球蛋白(IG)M和伊加的聚合,与其IG重链的C末端形成二硫键,并控制IgM/伊加跨粘膜上皮的转运。与IG和类人适应性免疫一样,J链也出现在有颌类脊椎动物中,但自50多年前被发现以来,其起源一直是个谜。在这里,我们意外地表明,J链是CXCL趋化因子家族的成员。J链基因(JCHAIN)与除失去JCHAIN的放线菌外的所有有颌类中的成簇CXCL趋化因子基因座连锁。JCHAIN和大多数CXCL基因具有四个外显子,其具有相同的内含子相位,包括信号肽/成熟蛋白的相同切割位点。这两个基因的第二外显子编码CXC基序,在相同的位置,和外显子1至3的长度相似。人类分泌组中没有其他基因具有所有这些特征。相比之下,两种蛋白质的链内二硫键完全不同,可能是由于J链中的修饰以指导IG聚合和粘膜转运。CXCL 8和J链的晶体结构共享保守的β链核心,但由于不同的链内二硫键和J链C末端的延伸而在其他方面有所不同。鉴定J链和CXCL趋化因子之间的这种祖先联系解决了免疫学中的一个古老问题。
The joining (J) chain regulates polymerization of multimeric Immunoglobulin(Ig)M and IgA, forming a disulfide bond to the C termini of their Ig heavy chains, and it controls IgM/IgA transport across mucosal epithelia. Like Ig itself and human-like adaptive immunity, J chain emerged in jawed vertebrates (gnathostomes), but its origin has remained mysterious since its discovery over 50 y ago. Here, we show unexpectedly that J chain is a member of the CXCL chemokine family. The J chain gene (JCHAIN) is linked to clustered CXCL chemokine loci in all gnathostomes except actinopterygians that lost JCHAIN. JCHAIN and most CXCL genes have four exons with the same intron phases, including the same cleavage site for the signal peptide/mature protein. The second exon of both genes encodes a CXC motif at the same position, and the lengths of exons 1 to 3 are similar. No other gene in the human secretome shares all of these characteristics. In contrast, intrachain disulfide bonds of the two proteins are completely different, likely due to modifications in J chain to direct Ig polymerization and mucosal transport. Crystal structures of CXCL8 and J chain share a conserved beta-strand core but diverge otherwise due to different intrachain disulfide bonds and extension of the J chain C terminus. Identification of this ancestral affiliation between J chain and CXCL chemokines addresses an age-old problem in immunology.
让 J 链重新出现在地图上:它的表达如何定义浆细胞的发育?
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