人胸腺基质淋巴细胞生成素中两个受体相互作用决定簇的功能表征
Functional characterisation of two receptor interaction determinants in human thymic stromal lymphopoietin.
作者信息
Marković Iva, Wolfrum Therese, Wohlmann Andreas, Gautam Kritan, Friedrich Karlheinz
机构信息
Institute of Biochemistry II, University Hospital Jena, Nonnenplan 2-4, D-07743 Jena, Germany.
出版信息
Biol Chem. 2021 Oct 26;403(2):243-249. doi: 10.1515/hsz-2021-0293. Print 2022 Jan 27.
Thymic stromal lymphopoietin (TSLP) is a pro-inflammatory cytokine with important pathological roles in , malignant tumours and other diseases. The heterodimeric human TSLP receptor (hTSLPR) consists of the TSLP-binding subunit (TSLPRα) and the IL-7Rα-subunit. We studied the properties of hTSLP variants with mutations in their bipartite interaction interface towards IL-7Rα. One mutant (T46D/K101D) showed only mild impairment in receptor affinity but a massive reduction in biological activity. To facilitate the future development of hTSLP mutants with drug properties, we have devised a eukaryontic cytokine display assay with activity read-out and intrinsic genotype-phenotype coupling.
胸腺基质淋巴细胞生成素（TSLP）是一种促炎细胞因子，在恶性肿瘤和其他疾病中具有重要的病理作用。人TSLP受体（hTSLPR）异二聚体由TSLP结合亚基（TSLPRα）和IL-7Rα亚基组成。我们研究了hTSLP变体的特性，这些变体在其与IL-7Rα的二分相互作用界面中发生了突变。一种突变体（T46D/K101D）仅表现出受体亲和力的轻度受损，但生物活性大幅降低。为了促进具有药物特性的hTSLP突变体的未来开发，我们设计了一种具有活性读出和内在基因型-表型偶联的真核细胞因子展示测定法。
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