Eisenberg S P, Brewer M T, Verderber E, Heimdal P, Brandhuber B J, Thompson R C
Synergen, Boulder, CO 80301.
Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5232-6. doi: 10.1073/pnas.88.12.5232.
Interleukin 1 receptor antagonist (IL-1ra) is a protein that binds to the IL-1 receptor and blocks the binding of both IL-1 alpha and -beta without inducing a signal of its own. Human IL-1ra has some sequence identity to human IL-1 beta, but the evolutionary relationship between these proteins has been unclear. We show that the genes for human, mouse, and rat IL-1ra are similar to the genes for IL-1 alpha and IL-1 beta in intron-exon organization, indicating that gene duplication events were important in the creation of this gene family. Furthermore, an analysis of sequence comparisons and mutation rates for IL-1 alpha, IL-1 beta, and IL-1ra suggests that the duplication giving rise to the IL-1ra gene was an early event in the evolution of the gene family. Comparisons between the mature sequences for IL-1ra, IL-1 alpha, and IL-1 beta suggest that IL-1ra has a beta-stranded structure like to IL-1 alpha and IL-1 beta, consistent with the three proteins being related. The N-terminal sequences of IL-1ra appear to be derived from a region of the genome different than those of IL-1 alpha and IL-1 beta, thus explaining their different modes of biosynthesis and suggesting an explanation for their different biological activities.
白细胞介素1受体拮抗剂（IL-1ra）是一种蛋白质，它与IL-1受体结合，阻断IL-1α和IL-1β的结合，而自身不诱导信号。人IL-1ra与人类IL-1β有一些序列同源性，但这些蛋白质之间的进化关系尚不清楚。我们发现，人、小鼠和大鼠IL-1ra的基因在基因内含子-外显子组织上与IL-1α和IL-1β的基因相似，这表明基因复制事件在这个基因家族的形成中很重要。此外，对IL-1α、IL-1β和IL-1ra的序列比较和突变率分析表明，产生IL-1ra基因的复制是该基因家族进化中的一个早期事件。对IL-1ra、IL-1α和IL-1β成熟序列的比较表明，IL-1ra具有与IL-1α和IL-1β相似的β链结构，这与这三种蛋白质相关一致。IL-1ra的N端序列似乎来自基因组中与IL-1α和IL-1β不同的区域，从而解释了它们不同的生物合成模式，并为它们不同的生物学活性提供了一种解释。
