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组装依赖的结构形成形状人类互乐金-23 与互乐金-12 分泌分泌

Isabel Aschenbrenner¹, Till Siebenmorgen², Abraham Lopez³

¹Technical University of Munich, TUM School of Natural Sciences, Department of Bioscience, Center for Functional Protein Assemblies (CPA), Garching, Germany.

Journal of molecular biology

|October 7, 2023

概括

研究人员设计了一种更稳定的IL-23α,可以自组装,改善IL-23的产生. 这表明自然的α子单元可能会演变为依赖组装的折叠来调节免疫反应.

科学领域:

免疫学免疫学免疫学
分子生物学分子生物学
蛋白质工程是指蛋白质工程.

背景情况:

介素-12 (IL-12) 细胞因子家族对免疫系统调节至关重要.
这些细胞因子作为α:β异构体起作用,α子单元通常需要β子单元才能进行适当的折叠和分泌.
家庭成员之间共享的β子单元,如IL-12和IL-23的β子单元,可以导致竞争并影响细胞因子平衡.

研究的目的:

为了设计一个具有折叠能力的人类IL-23α亚单元 (IL-23α),它独立于它的β亚单元来形成结构.
为了研究这个工程子单元是否可以形成具有改变组装特性的功能异构体细胞因子.
探索工程制造的α子单元对IL-12和IL-23生产平衡的影响.

主要方法:

使用蛋白质工程,合理设计人类IL-23α亚单元.
评估工程子单位的折叠能力和护送依赖度.
对异种体形成和细胞因子组合与β子单元的分析.
量化IL-12和IL-23的形成,以确定歪曲效应.

主要成果:

成功设计了一种能够折叠的人类IL-23α子单元.
这种变异表明伴侣的依赖性减少,对其β子单元的亲和力增加.
改造后的子单元组装效率更高,导致IL-23形成比IL-12增加.
很少有突变足以产生与细胞因子组合和功能相容的折叠能力的α子单元.

结论:

通过向突变,可以产生对IL-12家族具有折叠能力的α子单元.
改造的IL-23α增强了IL-23的产生,这表明免疫反应调节的潜在机制.
这些发现支持了这样一个假设:自然的α子单元可能已经进化为组装依赖的折叠,以调节在子单元竞争下的细胞因子比率.

关键词:

陪伴者 (chaperones) 是指一个陪伴者.它们包括interleukins.蛋白质组合组件的组合蛋白质折叠蛋白质的折叠蛋白质分泌蛋白质分泌蛋白质分泌

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