Paired receptor specificity explained by structures of signal regulatory proteins alone and complexed with CD47
Paired receptor specificity explained by structures of signal regulatory proteins alone and complexed with CD47
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DOI：
10.1016/j.molcel.2008.05.026
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发表时间：
2008-07-25
期刊：
影响因子：
16
通讯作者：
Barclay, A. Neil
中科院分区：
文献类型：
--
作者：
Hatherley, Deborah;Graham, Stephen C.;Barclay, A. Neil
CD47是一种广泛分布的细胞表面蛋白，通过髓系细胞和神经细胞的相互作用而成为自身的标志。我们描述了CD47的免疫球蛋白超家族结构域单独以及与信号调节蛋白α的N末端配体结合结构域(SIRPα)的高分辨X射线晶体结构。CD47的不寻常和复杂的相互作用面，包括结构域末端的N末端和环，与SIRPα中的相应区域插入。我们还确定了SIRPβ、SIRPβ(2)和SIRP Gamma；蛋白的N-末端结构域的结构，这些蛋白与SIRα密切相关，但与CD47的亲和力可忽略或降低。这些结果从原子细节上解释了CD47对SIRP家族受体的特异性。对SIRPα多态的分析表明，这些以及激活的SIRP可能已经进化成对抗病原体与抑制性SIRPα受体的结合。
CD47 is a widely distributed cell-surface protein that acts a marker of self through interactions of myeloid and neural cells. We describe the high-resolution Xray crystallographic structures of the immunoglobulin superfamily domain of CD47 alone and in complex with the N-terminal ligand-binding domain of signal regulatory protein alpha (SIRP alpha). The unusual and convoluted interacting face of CD47, comprising the N terminus and loops at the end of the domain, intercalates with the corresponding regions in SIRP alpha. We have also determined structures of the N-terminal domains of SIRP beta, SIRP beta(2), and SIRP gamma; proteins that are closely related to SIR alpha but bind CD47 with negligible or reduced affinity. These results explain the specificity of CD47 for the SIRP family of paired receptors in atomic detail. Analysis of SIRP alpha polymorphisms suggests that these, as well as the activating SIRPs, may have evolved to counteract pathogen binding to the inhibitory SIRP alpha receptor.