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首页> 外文期刊>Molecular and Cellular Biology >Ligand-induced association of the type I interferon receptor components.
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Ligand-induced association of the type I interferon receptor components.

机译:配体诱导的I型干扰素受体组分的缔合。

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Two transmembrane polypeptides, IFNAR and IFN-alpha/Beta R, were previously identified as essential components of the type I interferon (IFN) receptor, but their interrelationship and role in ligand binding were not clear. To study these issues, we stably expressed and characterized the two polypeptides in host murine cells. In human cells, native IFN-alpha/beta R is a 102-kDa protein but upon reduction only a 51-kDa protein is detected. In host murine cells human IFN-alpha/beta R was expressed as a 51-kDa protein. Host cells expressing IFN-alpha/beta R bound IFN-alpha 2 with a high affinity (Kd of 3.6 nM), whereas cells expressing IFNAR exhibited no ligand binding. Upon coexpression of IFNAR and the 51-kDa IFN-alpha/beta R, the affinity for IFN-alpha 2 was increased 10-fold, approaching that of the native receptor. We show by cross-linking that both the cloned (51-kDa) and native (102-kDa) IFN-alpha/beta R bind IFN-alpha 2 to form an intermediate product, while IFNAR associates with this product to form a ternary complex. Hence, IFNAR and IFN-alpha/beta R are components of a common type I IFN receptor, cooperating in ligand binding. Ligand-induced association of IFNAR and IFN-alpha/beta R probably triggers transmembrane signaling.
机译:先前已将两种跨膜多肽IFNAR和IFN-α/ Beta R鉴定为I型干扰素(IFN)受体的必需成分,但它们之间的相互关系和在配体结合中的作用尚不清楚。为了研究这些问题,我们在宿主鼠细胞中稳定表达并鉴定了这两种多肽。在人类细胞中,天然IFN-α/βR是一种102 kDa的蛋白质,但还原后仅检测到51 kDa的蛋白质。在宿主鼠细胞中,人IFN-α/βR被表达为51-kDa蛋白。表达IFN-α/βR的宿主细胞以高亲和力(Kd为3.6 nM)结合IFN-α2,而表达IFNAR的细胞则没有配体结合。在IFNAR和51-kDaIFN-α/βR共表达后,对IFN-α2的亲和力增加了10倍,接近天然受体的亲和力。我们通过交联显示,克隆的(51-kDa)和天然的(102-kDa)IFN-α/βR都结合IFN-alpha 2形成中间产物,而IFNAR与该产物缔合形成三元复合物。因此,IFNAR和IFN-α/βR是共同的I型IFN受体的组分,在配体结合中协同作用。配体诱导的IFNAR和IFN-α/βR缔合可能触发跨膜信号传导。

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