Structural diversity of the hagfish variable lymphocyte receptors
Structural diversity of the hagfish variable lymphocyte receptors
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DOI：
10.1074/jbc.m608471200
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发表时间：
2007-03-02
影响因子：
4.8
通讯作者：
Lee, Jie-Oh
中科院分区：
文献类型：
--
作者：
Kim, Ho Min;Oh, Se Cheol;Lee, Jie-Oh
可变淋巴细胞受体（VLRs）是近年来发现的一种富含亮氨酸重复序列（LRR）家族蛋白，在无颌鱼类中介导适应性免疫反应。在系统发育上，它是最古老的适应性免疫受体，也是第一个具有非免疫球蛋白折叠的受体。我们提出了一个VLR-A和两个VLR-B克隆从近海盲鳗的晶体结构。盲鳗类VLRs具有LRR家族蛋白的特征性马蹄形结构。它们的LRR模块的骨架结构高度同源，序列变异集中在蛋白质的凹面上。关键残基的保护表明，我们的结构很可能代表整个库的无颌鱼VLRs的LRR结构。序列变异性分析、蛋白质相互作用表面预测、氨基酸组成分析以及与其他LRR蛋白的结构比较表明，高变凹面是VLR最可能的抗原结合位点。
Variable lymphocyte receptors (VLRs) are recently discovered leucine-rich repeat (LRR) family proteins that mediate adaptive immune responses in jawless fish. Phylogenetically it is the oldest adaptive immune receptor and the first one with a non-immunoglobulin fold. We present the crystal structures of one VLR-A and two VLR-B clones from the inshore hagfish. The hagfish VLRs have the characteristic horseshoe-shaped structure of LRR family proteins. The backbone structures of their LRR modules are highly homologous, and the sequence variation is concentrated on the concave surface of the protein. The conservation of key residues suggests that our structures are likely to represent the LRR structures of the entire repertoire of jawless fish VLRs. The analysis of sequence variability, prediction of protein interaction surfaces, amino acid composition analysis, and structural comparison with other LRR proteins suggest that the hypervariable concave surface is the most probable antigen binding site of the VLR.