title: Solution structure of S. cerevisiae PDCD5-like protein and its promoting role in H(2)O(2)-induced apoptosis in yeast.
abstract: 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.
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei 230027, PR China.
authors.forename: Jingjun
authors.initials: J
authors.lastname: Hong
authors.forename: Jiahai
authors.initials: J
authors.lastname: Zhang
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Liu
authors.forename: Su
authors.initials: S
authors.lastname: Qin
authors.forename: Jihui
authors.initials: J
authors.lastname: Wu
authors.forename: Yunyu
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000595:Amino Acid Sequence; D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D015153:Blotting, Western; D002942:Circular Dichroism; D004247:DNA; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D013056:Spectrophotometry, Ultraviolet; D013113:Spin Labels
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D013113:Spin Labels; D004247:DNA; D006861:Hydrogen Peroxide