T cell immunoglobulin mucin-3 crystal structure reveals a galectin-9-independent ligand-binding surface
T cell immunoglobulin mucin-3 crystal structure reveals a galectin-9-independent ligand-binding surface
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DOI：
10.1016/j.immuni.2007.01.016
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发表时间：
2007-03-01
期刊：
影响因子：
32.4
通讯作者：
Almo, Haiteng C.
中科院分区：
文献类型：
--
作者：
Cao, Erhu;Zang, Xingxing;Almo, Haiteng C.
T细胞免疫球蛋白粘蛋白（Tim）受体家族调节效应CD 4（+）T细胞功能，并与自身免疫性和过敏性疾病有关。Tim-3诱导免疫耐受，并且Tim-3免疫球蛋白可变（IgV）结构域与半乳糖凝集素-9的接合对于适当终止T辅助细胞1免疫应答是重要的。Tim-3 IgV结构域的2埃晶体结构表明，Tim家族中不变的四个半胱氨酸形成两个非典型的二硫键，导致表面不存在于其他免疫球蛋白超家族成员中。生物化学和生物物理学研究表明，这种独特的结构特征介导了以前未鉴定的半乳糖凝集素-9-独立的结合过程，并表明这种结构特征在整个Tim家族中是保守的。目前的工作提供了序列，结构和功能之间的关系的一个图形的例子，并建议多种Tim-3结合活性之间的相互作用有助于调节组装的信号复合物所需的有效的Th 1介导的免疫。
The T cell immunoglobulin mucin (Tim) family of receptors regulates effector CD4(+) T cell functions and is implicated in autoimmune and allergic diseases. Tim-3 induces immunological tolerance, and engagement of the Tim-3 immunoglobulin variable (IgV) domain by galectin-9 is important for appropriate termination of T helper 1-immune responses. The 2 angstrom crystal structure of the Tim-3 IgV domain demonstrated that four cysteines, which are invariant within the Tim family, form two noncanonical disulfide bonds, resulting in a surface not present in other immunoglobulin superfamily members. Biochemical and biophysical studies demonstrated that this unique structural feature mediates a previously unidentified galectin-9-independent binding process and suggested that this structural feature is conserved within the entire Tim family. The current work provided a graphic example of the relationship between sequence, structure, and function and suggested that the interplay between multiple Tim-3-binding activities contributes to the regulated assembly of signaling complexes required for effective Th1-mediated immunity.