Solution Structure of S. cerevisiae PDCD5-Like Protein and Its Promoting Role in H2O2-Induced Apoptosis in Yeast
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- 作者：Jingjun Hong ; Jiahai Zhang ; Zhijun Liu ; Su Qin ; Jihui Wu ; Yunyu Shi
- 刊名：Biochemistry
- 出版年：2009
- 出版时间：July 28, 2009
- 年：2009
- 卷：48
- 期：29
- 页码：6824-6834
- 全文大小：1100K
- 年卷期：v.48,no.29(July 28, 2009)
- ISSN：1520-4995
文摘
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 α-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 H2O2-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.