The structure of the macrophage signal regulatory protein α (SIRPα) inhibitory receptor reveals a binding face reminiscent of that used by T cell receptors
The structure of the macrophage signal regulatory protein α (SIRPα) inhibitory receptor reveals a binding face reminiscent of that used by T cell receptors
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DOI：
10.1074/jbc.m611511200
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发表时间：
2007-05-11
影响因子：
4.8
通讯作者：
Barclay, A. Neil
中科院分区：
文献类型：
--
作者：
Hatherley, Deborah;Harlos, Karl;Barclay, A. Neil
信号调节蛋白（SIRP）α是一种膜受体，通过与CD 47结合向骨髓细胞发送抑制信号。N-末端配体结合结构域的高分辨率X射线结构显示其具有独特的免疫球蛋白超家族V样折叠。定点诱变表明，CD 47结合在涉及BC、FG和DE环的表面，这将其与使用折叠面但类似于抗原受体的其他免疫球蛋白超家族表面蛋白区分开来。SIRP相互作用仅限于单个结构域，并且其延长的DE环的使用加强了与T细胞受体结合的相似性以及它们在进化中密切相关的暗示。使用环形成CD 47结合表面提供了小序列变化调节结合特异性的机制，解释了SIRP家族成员的不同结合特性。
Signal regulatory protein ( SIRP) alpha is a membrane receptor that sends inhibitory signals to myeloid cells by engagement of CD47. The high resolution x-ray structure of the N-terminal ligand binding domain shows it to have a distinctive immunoglobulin superfamily V-like fold. Site-directed mutagenesis suggests that CD47 is bound at a surface involving the BC, FG, and DE loops, which distinguishes it from other immunoglobulin superfamily surface proteins that use the faces of the fold, but resembles antigen receptors. The SIRP interaction is confined to a single domain, and its use of an extended DE loop strengthens the similarity with T cell receptor binding and the suggestion that they are closely related in evolution. The employment of loops to form the CD47-binding surface provides a mechanism for small sequence changes to modulate binding specificity, explaining the different binding properties of SIRP family members.