Crystal structure of the human myeloid cell activating receptor TREM-1
Crystal structure of the human myeloid cell activating receptor TREM-1
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DOI：
10.1016/j.str.2003.11.001
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发表时间：
2003-12-01
期刊：
影响因子：
5.7
通讯作者：
Sun, PD
中科院分区：
文献类型：
--
作者：
Radaev, S;Kattah, M;Sun, PD
髓样细胞上表达的触发受体（TREM）是最近发现的受体家族，其在先天性免疫应答中发挥重要作用，例如激活炎症应答并响应于微生物介导的感染而促成败血性休克。迄今为止，已经鉴定了人中的两种TREM受体和小鼠中的几种同源物。我们报告了人TREM-1胞外结构域的2.6埃分辨率晶体结构。受体的总体折叠类似于V型免疫球蛋白结构域，差异主要位于N-末端链。TREM-1形成具有4100埃（2）界面面积的“头-尾”二聚体，其部分由第一链之间的结构域交换介导。这种二聚体形成模式不同于抗体的VHVL结构域或T细胞受体的V结构域中存在的“头对头”二聚化。因此，二聚体TREM-1很可能含有两个不同的配体结合位点。
Triggering receptors expressed on myeloid cells (TREM) are a family of recently discovered receptors that play important roles in innate immune responses, such as to activate inflammatory responses and to contribute to septic shock in response to microbial-mediated infections. To date, two TREM receptors in human and several homologs in mice have been identified. We report the 2.6 Angstrom resolution crystal structure of the extracellular domain of human TREM-1. The overall fold of the receptor resembles that of a V-type immunoglobulin domain with differences primarily located in the N-terminal strand. TREM-1 forms a "head-to-tail" dimer with 4100 Angstrom(2) interface area that is partially mediated by a domain swapping between the first strands. This mode of dimer formation is different from the "head-to-head" dimerization that existed in VHVL domains of antibodies or V domains of T cell receptors. As a result, the dimeric TREM-1 most likely contains two distinct ligand binding sites.