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通过特定的S100蛋白质识别颗粒细胞-巨细胞殖民地刺激因子

Alexey S Kazakov¹, Victoria A Rastrygina¹, Alisa A Vologzhannikova¹

¹Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences, Institute for Biological Instrumentation, Institutskaya str., 7, Pushchino, Moscow Region 142290, Russia.

|March 14, 2024

概括

S100A4蛋白特别与颗粒细胞-巨细胞殖民地刺激因子 (GM-CSF) 结合,调节其信号传递. 这种相互作用取决于和蛋白质结构,影响细胞活力和疾病进展,提供新的治疗点.

科学领域:

生物化学生物化学
免疫学免疫学免疫学
分子生物学分子生物学

背景情况:

颗粒细胞-巨细胞殖民地刺激因子 (GM-CSF) 是免疫反应和血液形成中的关键细胞因子.
转基因-CSF是各种疾病的治疗点,包括癌症和自身免疫性疾病.
S100蛋白是一种具有多种细胞功能的结合蛋白家族.

研究的目的:

研究GM-CSF与各种S100蛋白之间的特定结合相互作用.
描述影响S100蛋白与GM-CSF结合的亲和力和条件.
探索S100蛋白与GM-CSF信号交互的功能后果.

主要方法:

表面等离子体共振光谱测量结合亲和力.
内在的光和化学交叉连接来确认相互作用.
位点定向突变发生和结构建模以确定结合位点.
细胞活力测试用于评估对GM-CSF信号传递的功能影响.

主要成果:

S100A4蛋白与高亲和力 (K_d 0.3-2 μM) 特别结合GM-CSF.
结合是依赖的,对S100蛋白质单化敏感.
确定了S100A4 / A6 / P的GM-CSF上保存的结合部位,涉及对受体相互作用也很重要的残留物.
S100A4和S100A6抑制了GM-CSF诱导的单细胞细胞活性的抑制.

结论:

S100A4是GM-CSF的特定约束性合作伙伴,与之前识别的S100A6和S100P不同.
S100蛋白和GM-CSF之间的相互作用直接调节GM-CSF信号通路.
这些发现对了解GM-CSF在疾病中的作用以及开发针对GM-CSF信号的新疗法有意义.

关键词:

细胞活力细胞活力转基因-CSFF是什么意思蛋白质蛋白质相互作用在 S100A4 中使用.在S100A6A6中使用.在S100P中,它是S100P.

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