Crystal structure of the lamprey variable lymphocyte receptor C reveals an unusual feature in its N-terminal capping module.

Crystal structure of the lamprey variable lymphocyte receptor C reveals an unusual feature in its N-terminal capping module.
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DOI:
10.1371/journal.pone.0085875
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Ose T
Ose T
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Kanda R;Sutoh Y;Kasamatsu J;Maenaka K;Kasahara M;Ose T

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以七鳃鳗和八目鳗为代表的无颌脊椎动物使用可变淋巴细胞受体(VLR)作为抗原受体来产生适应性免疫反应。VLR通过由胞嘧啶脱氨酶介导的基因转化样机制产生与免疫球蛋白和T细胞受体相当的多样性。目前,已在七鳃鳗中鉴定出三种类型的VLRs,VLRA、VLRB和VLRC。VLRA和VLRB与抗原复合物的晶体结构最近已被报道,但没有VLRC的结构信息。在这里,我们提出了第一个晶体结构的VLRC从日本七鳃鳗(Lethenteron japonicum)。与VLRA和VLRB类似,VLRC形成具有可变凹面的典型马蹄形螺线管结构。引人注目的是,其N-末端帽具有向凹面突出的具有有限序列可变性的长环,凹面是推定的抗原结合表面。此外,如前所述,其C端帽缺乏高度可变的突出环,该突出环在七鳃鳗VLRA和VLRB的抗原识别中起重要作用。最近的研究表明,无颌脊椎动物中的VLRC+淋巴细胞可能类似于有颌脊椎动物中的γδ T细胞。这里描述的七鳃鳗VLRC的结构特征表明,它可能以独特的方式识别抗原。
Jawless vertebrates represented by lampreys and hagfish use variable lymphocyte receptors (VLRs) as antigen receptors to mount adaptive immune responses. VLRs generate diversity that is comparable to immunoglobulins and T-cell receptors by a gene conversion-like mechanism, which is mediated by cytosine deaminases. Currently, three types of VLRs, VLRA, VLRB, and VLRC, have been identified in lampreys. Crystal structures of VLRA and VLRB in complex with antigens have been reported recently, but no structural information is available for VLRC. Here, we present the first crystal structure of VLRC from the Japanese lamprey (Lethenteron japonicum). Similar to VLRA and VLRB, VLRC forms a typical horseshoe-like solenoid structure with a variable concave surface. Strikingly, its N-terminal cap has a long loop with limited sequence variability that protrudes toward the concave surface, which is the putative antigen-binding surface. Furthermore, as predicted previously, its C-terminal cap lacks a highly variable protruding loop that plays an important role in antigen recognition by lamprey VLRA and VLRB. Recent work suggests that VLRC+ lymphocytes in jawless vertebrates might be akin to γδ T cells in jawed vertebrates. Structural features of lamprey VLRC described here suggest that it may recognize antigens in a unique manner.
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