相关实验视频
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Transmembrane Domain Oligomerization Propensity determined by ToxR Assay
Published on: May 26, 2011
人类TRAF2自我关联和受体识别的结构基础
Y C Park1, V Burkitt, A R Villa
1Department of Biochemistry, The Weill Medical College and Graduate School of Medical Sciences of Cornell University, New York, New York 10021, USA.
Nature
|April 17, 1999
概括
瘤亡因子 (TNF) - 受体相关因子 (TRAFs) 是关键的适应蛋白. 它们的TRAF2域结构揭示了三元组合,解释了受体如何招募TRAF用于细胞信号传递.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 免疫学 免疫学 免疫学
背景情况:
- 瘤坏死因子 (TNF) - 受体相关因子 (TRAFs) 是细胞质适配蛋白,对于来自TNF受体超级家族和互白素-1受体的信号传导至关重要.
- TRAFs调节重要的细胞过程,包括细胞存活和细胞死亡.
- 对于自我关联和受体相互作用至关重要的碳氧终端TRAF域,包含一个卷积-卷积区域和一个保存的TRAF-C域.
研究的目的:
- 为了确定人类TRAF2.2的TRAF域的晶体结构.
- 为了研究TRAF2 TRAF域与TNF受体-2 (TNF-R2) 的酸之间的复杂形成.
- 阐明TRAF2自我结合和受体结合的结构基础.
主要方法:
- 使用X射线晶体学来确定单独的人类TRAF2的TRAF域的结构,以及与TNF-R2的复合物.
- 使用基于溶液的研究来证实在晶体结构中观察到的三元体自我关联.
主要成果:
- 晶体结构揭示了TRAF2 TRAF域的三元自我关联.
- TRAF-C域采用了一种新的八链反平行β三明治折叠.
- TNF-R2与单个TRAF-C原体上的浅表面沉结合,这表明SXXE基因是潜在的TRAF2-结合共识序列.
结论:
- TRAF域的三聚体结构为TRAF招募提供了一个基于激情的机制,这取决于三聚体配体对受体的寡合化.
- 这种结构性洞察对于理解TNF受体超级家族信号通路至关重要.
- 这些发现为TRAF2在调节细胞生存和死亡途径中的作用提供了分子基础.
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