Solution structure of S. cerevisiae PDCD5-like protein and its promoting role in H(2)O(2)-induced apoptosis in yeast.
Solution structure of S. cerevisiae PDCD5-like protein and its promoting role in H(2)O(2)-induced apoptosis in yeast.
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DOI：
10.1021/bi900488n
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发表时间：
2009-07
期刊：
影响因子：
2.9
通讯作者：
Jingjun Hong;Jiahai Zhang;Zhijun Liu;S. Qin;Jihui Wu;Yunyu Shi
中科院分区：
文献类型：
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作者：
Jingjun Hong;Jiahai Zhang;Zhijun Liu;S. Qin;Jihui Wu;Yunyu Shi
人PDCD5蛋白是一种新的程序性细胞死亡促进分子。然而，与hPDCD5同源的酿酒葡萄球菌Ymr074cP的功能尚不清楚。采用异核磁共振法测定了Ymr074cP蛋白n端116残基片段（N116）的溶液结构。N116被证明是一个灵活折叠构象的异质集合，采用扩展的三螺旋束折叠，通过一个长而高柔性的连接子连接到n端可移动但结构化的α -螺旋。通过附着在突变体7或11位半胱氨酸残基上的氮氧化物自旋标记，在n端螺旋部分和核心部分以及c端尾部的几个残基之间探测到显著的瞬态相互作用。三螺旋束的拓扑结构主要由疏水相互作用编码，n端螺旋结构具有独特的静电电位特征。对pdcd5相关蛋白溶液结构的比较表明，三螺旋束的结构在进化过程中具有明显的保守性。我们首次证明YMR074c过表达促进酵母中H(2)O(2)诱导的细胞凋亡，不仅以依赖于yca1的方式，而且以不依赖于yca1的方式，并且n端螺旋部分的缺失大大减弱了该蛋白的促凋亡活性。
Human PDCD5 protein is a novel programmed cell death-promoting molecule. However, the function of Ymr074cP, a S. cerevisiae homologue of hPDCD5, is still unknown. Heteronuclear NMR methods were used to determine the solution structure of the N-terminal 116-residue fragment (N116) of Ymr074cP protein. N116 is shown to be a heterogeneous ensemble of flexibly folded conformations, adopting an extended triple-helix bundle fold that is connected to a mobile but structured alpha-helix in the N-terminus by means of a lengthy highly flexible linker. By the nitroxide spin label, attached to the mutant cysteine residue at position 7 or 11, significant transient interactions were probed between the N-terminal helical portion and the core moiety plus several residues in the C-terminal tail. The topology of the triple-helix bundle is encoded mainly by hydrophobic interactions, and the N-terminal helical structure has a unique electrostatic potential character. A comparison of the solution structures of PDCD5-related proteins indicates that the structure of the triple-helix bundle is significantly conserved during evolution. We are the first to demonstrate that YMR074c overexpression promotes H(2)O(2)-induced apoptosis in yeast, not only in a metacaspase Yca1-dependent manner but also in a Yca1-independent manner and that deletion of the N-terminal helical portion greatly attenuates the apoptosis-promoting activity of this protein.