Structural basis of cargo membrane protein discrimination by the human COPII coat machinery.
Structural basis of cargo membrane protein discrimination by the human COPII coat machinery.
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人类Copii外套机制的货物膜蛋白歧视的结构基础。
DOI：
10.1038/emboj.2008.208
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发表时间：
2008-11-05
期刊：
影响因子：
11.4
通讯作者：
Goldberg, Jonathan
中科院分区：
文献类型：
--
作者：
Mancias, Joseph D.;Goldberg, Jonathan
基因组分析表明，哺乳动物细胞中运输途径的复杂性增加涉及SNARE、Rab和COP蛋白数量的扩增。因此，人类基因组编码四种形式的Sec24，COPII囊泡外壳的货物选择亚基，这被认为是为了增加人类COPII包被囊泡容纳的货物范围。在这项研究中，我们结合了X射线晶体学和生化分析与货物包装到COPII囊泡的功能测定，以建立人类Sec24亚基货物歧视的分子机制。保守的IxM包装信号结合在Sec24c和Sec24d的表面沟中，但该沟在Sec24a和Sec24b亚基中被封闭。相反，VSV糖蛋白的LxxLE类转运信号和DxE信号选择性地与Sec24 a和Sec24 b亚基结合。四个人类Sec24亚型的晶体结构的比较分析建立了这些运输信号之间的歧视的结构决定因素，并提供了一个框架，以了解如何扩展的外壳亚基扩展的货物蛋白包装到COPII包被囊泡的范围。
Genomic analysis shows that the increased complexity of trafficking pathways in mammalian cells involves an expansion of the number of SNARE, Rab and COP proteins. Thus, the human genome encodes four forms of Sec24, the cargo-selection subunit of the COPII vesicular coat, and this is proposed to increase the range of cargo accommodated by human COPII-coated vesicles. In this study, we combined X-ray crystallographic and biochemical analysis with functional assays of cargo packaging into COPII vesicles to establish molecular mechanisms for cargo discrimination by human Sec24 subunits. A conserved IxM packaging signal binds in a surface groove of Sec24c and Sec24d, but the groove is occluded in the Sec24a and Sec24b subunits. Conversely, LxxLE-class transport signals and the DxE signal of VSV glycoprotein are selectively bound by Sec24a and Sec24b subunits. A comparative analysis of crystal structures of the four human Sec24 isoforms establishes the structural determinants for discrimination among these transport signals, and provides a framework to understand how an expansion of coat subunits extends the range of cargo proteins packaged into COPII-coated vesicles.
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