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首页> 外文期刊>Cytokine >The c.305del3 in IL-2 gene in Homonoidea theoretically affects IL-2/IL-2R alpha interaction as well as lymphocyte homeostasis
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The c.305del3 in IL-2 gene in Homonoidea theoretically affects IL-2/IL-2R alpha interaction as well as lymphocyte homeostasis

机译：Homanoidea中IL-2基因中的C.305DEL3理论上影响了IL-2 / IL-2Rα相互作用以及淋巴细胞稳态

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摘要

Interleukin-2 (IL-2) is a well-known monomeric T-cell growth factor that is produced primarily by activated CD4+ T cells following exposure to antigen. IL-2 structural analysis among primates showed a few polymorphisms as well as a 3-nucleotide deletion (c.305del3) in Hominoidea superfamily including Homo sapiens. On the other hand, the interaction of IL-2 with its alpha subunit of the receptor (IL-2R alpha) is the first step for assembly of the whole IL-2R and considered as a species-specific phase. Four models of human IL-2, IL-2R alpha, and their ancestral forms were made and were used for molecular dynamics (MD) simulation. Subsequently, the final structures were docked to each other and finally, the complexes were used for MD simulation. Our results showed that the above mentioned deletion led to weaker interaction of human IL-2 to its receptor relative to ancestral IL-2. Association study of lymphocyte counts, as an indicator of IL-2 function, in 78 primate species with or without this deletion showed significant association of this deletion with their overall lymphocyte counts (P.01). Therefore, it can be suggested that p.81delThr in IL-2 in Hominides superfamily interfered with interaction of IL-2 and IL-2R alpha and led to overall decrease in lymphocyte counts in this superfamily of primates in comparison with other primates.
机译：白细胞介素-2（IL-2）是众所周知的单体T细胞生长因子，其主要通过暴露于抗原后的活化的CD4 + T细胞生产。制灵线的IL-2结构分析显示出几种多态性以及Hominoidea超家族的3核苷酸缺失（C.305del3），包括Homo Sapiens。另一方面，IL-2与受体（IL-2Rα）的α亚基的相互作用是组装整个IL-2R并被认为是特异性相的第一步骤。进行了四种型号的人IL-2，IL-2Rα及其祖先形式，用于分子动力学（MD）模拟。随后，最终结构彼此停靠，最后，将配合物用于MD模拟。我们的研究结果表明，上述缺失导致人IL-2相对于祖先IL-2对其受体的相互作用较弱。淋巴细胞计数的关联研究，作为IL-2功能的指标，在​​78个具有或没有这种缺失的灵长类动物中，表现出这种缺失与整个淋巴细胞计数的显着关联（P <.01）。因此，可以建议在母体中的IL-2中的p.81deltr，与IL-2和IL-2Rα的相互作用相互作用，并导致该Superfamily的淋巴细胞计数与其他灵长类相比，该超法中的淋巴细胞计数。

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