Hatherley Deborah, Graham Stephen C, Harlos Karl, Stuart David I, Barclay A Neil
Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom.
J Biol Chem. 2009 Sep 25;284(39):26613-9. doi: 10.1074/jbc.M109.017566. Epub 2009 Jul 23.
Signal-regulatory protein alpha (SIRPalpha) is a myeloid membrane receptor that interacts with the membrane protein CD47, a marker of self. We have solved the structure of the complete extracellular portion of SIRPalpha, comprising three immunoglobulin superfamily domains, by x-ray crystallography to 2.5 A resolution. These data, together with previous data on the N-terminal domain and its ligand CD47 (possessing a single immunoglobulin superfamily domain), show that the CD47-SIRPalpha interaction will span a distance of around 14 nm between interacting cells, comparable with that of an immunological synapse. The N-terminal (V-set) domain mediates binding to CD47, and the two others are found to be constant (C1-set) domains. C1-set domains are restricted to proteins involved in vertebrate antigen recognition: T cell antigen receptors, immunoglobulins, major histocompatibility complex antigens, tapasin, and beta2-microglobulin. The domains of SIRPalpha (domains 2 and 3) are structurally more similar to C1-set domains than any cell surface protein not involved in antigen recognition. This strengthens the suggestion from sequence analysis that SIRP is evolutionarily closely related to antigen recognition proteins.
信号调节蛋白α（SIRPα）是一种髓系膜受体，可与膜蛋白CD47（自身标记物）相互作用。我们通过X射线晶体学以2.5埃的分辨率解析了SIRPα完整胞外部分的结构，该部分由三个免疫球蛋白超家族结构域组成。这些数据，连同先前关于N端结构域及其配体CD47（具有单个免疫球蛋白超家族结构域）的数据表明，CD47-SIRPα相互作用在相互作用的细胞之间跨越的距离约为14纳米，与免疫突触的距离相当。N端（V-set）结构域介导与CD47的结合，另外两个是恒定（C1-set）结构域。C1-set结构域仅限于参与脊椎动物抗原识别的蛋白质：T细胞抗原受体、免疫球蛋白、主要组织相容性复合体抗原、塔帕辛和β2-微球蛋白。与任何不参与抗原识别的细胞表面蛋白相比，SIRPα的结构域（结构域2和3）在结构上与C1-set结构域更相似。这强化了序列分析得出的SIRP在进化上与抗原识别蛋白密切相关的观点。
