The structure of the extracellular domain of triggering receptor expressed on myeloid cells like transcript-1 and evidence for a naturally occurring soluble fragment
The structure of the extracellular domain of triggering receptor expressed on myeloid cells like transcript-1 and evidence for a naturally occurring soluble fragment
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DOI：
10.1074/jbc.m600489200
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发表时间：
2006-05-12
影响因子：
4.8
通讯作者：
Lubkowski, J
中科院分区：
文献类型：
--
作者：
Gattis, JL;Washington, AV;Lubkowski, J
骨髓细胞上表达的触发受体（如转录物-1 (TLT-1)）是一种丰富的血小板特异性 I 型跨膜受体。 TLT-1 的胞外片段由单个免疫球蛋白样结构域组成，通过称为茎的连接区与血小板细胞膜相连。在这里，我们提供的证据表明，在人类和小鼠的血清中发现了 TLT-1 胞外结构域的可溶性片段，并且在用凝血酶激活后，血小板中释放出类似质量的亚型。我们还报告了在 1.19 埃分辨率下测定的 TLT-1 免疫球蛋白结构域的晶体结构。 TLT-1的结构与其他免疫球蛋白样可变结构域相似，特别是骨髓细胞上表达的触发受体-1 (TREM-1)、自然杀伤细胞激活受体NKp44和聚合免疫球蛋白受体的结构域。特别令人感兴趣的是TLT-1的17个氨基酸片段，与鼠TREM-1的片段同源，其反过来显示出阻断小鼠中TREM-1介导的炎症反应的活性。与 TREM-1 和聚合免疫球蛋白受体的结构相似性，以及 TLT-1 胞外结构域天然存在的可溶性片段的证据表明，这种免疫球蛋白样结构域自主地发挥着尚未鉴定的功能作用。
Triggering receptor expressed on myeloid cells like transcript- 1 ( TLT- 1) is an abundant platelet- specific, type I transmembrane receptor. The extracellular fragment of TLT- 1 consists of a single, immunoglobulin- like domain connected to the platelet cell membrane by a linker region called the stalk. Here we present evidence that a soluble fragment of the TLT- 1extracellular domain is found in serum of humans and mice and that an isoform of similar mass is released from platelets following activation with thrombin. We also report the crystal structure of the immunoglobulin domain of TLT- 1 determined at the resolution of 1.19 angstrom. The structure of TLT- 1 is similar to other immunoglobulin- like variable domains, particularly those of triggering receptor expressed on myeloid cells- 1 ( TREM- 1), the natural killer cell- activating receptor NKp44, and the polymeric immunoglobulin receptor. Particularly interesting is a 17- amino acid segment of TLT- 1, homologous to a fragment of murine TREM- 1, which, in turn, showed activity in blocking the TREM- 1- mediated inflammatory responses in mice. Structural similarity to TREM- 1and polymeric immunoglobulin receptor, and evidence for a naturally occurring soluble fragment of the TLT- 1 extracellular domain, suggest that this immunoglobulin- like domain autonomously plays an as yet unidentified, functional role.