| Structural highlights
Function
MCA1_YEAST Mediates cell death (apoptosis) triggered by oxygen stress, salt stress or chronological aging. Regulated cell death can prevent a release of toxic cellular components, thus avoiding necrotic collapse of the colony, and can also provide nutrients for healthy cells. Therefore, regulated cell death in yeast colonies can be as important for their development as are apoptosis and related processes that occur within metazoa. Promotes the removal of insoluble protein aggregates during normal growth.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11]
Publication Abstract from PubMed
Yca1, the only metacaspase in Saccharomyces cerevisiae, is thought to be a clan CD cysteine protease that includes the caspase subfamily. Although yeast is a single cell eukaryote, it can undergo a cell death process reminiscent of apoptosis. Yca1 has been reported to play an important role in the regulation of such apoptotic process. However, the structure and functional mechanism of Yca1 remain largely enigmatic. In this study, we report the crystal structure of the Yca1 metacaspase at 1.7 A resolution, confirming a caspase-like fold. In sharp contrast to canonical caspases, however, Yca1 exists as a monomer both in solution and in the crystals. Canonical caspase contains six beta-strands, with strand beta6 pairing up with beta6 of another caspase molecule to form a homodimerization interface. In Yca1, an extra pair of antiparallel beta-strands forms a continuous beta-sheet with the six caspase-common beta-strands, blocking potential dimerization. Yca1 was reported to undergo autocatalytic processing in yeast; overexpression in bacteria also led to autoprocessing of Yca1 into two fragments. Unexpectedly, we found that both the autocatalytic processing and the proteolytic activity of Yca1 are greatly facilitated by the presence of calcium (Ca(2+)), but not other divalent cations. Our structural and biochemical characterization identifies Yca1 as a Ca(2+)-activated cysteine protease that may cleave specific substrates during stress response in yeast.
Crystal structure of the yeast metacaspase Yca1.,Wong AH, Yan C, Shi Y J Biol Chem. 2012 Aug 24;287(35):29251-9. doi: 10.1074/jbc.M112.381806. Epub 2012, Jul 2. PMID:22761449[12]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Madeo F, Herker E, Maldener C, Wissing S, Lachelt S, Herlan M, Fehr M, Lauber K, Sigrist SJ, Wesselborg S, Frohlich KU. A caspase-related protease regulates apoptosis in yeast. Mol Cell. 2002 Apr;9(4):911-7. PMID:11983181
- ↑ Bettiga M, Calzari L, Orlandi I, Alberghina L, Vai M. Involvement of the yeast metacaspase Yca1 in ubp10Delta-programmed cell death. FEMS Yeast Res. 2004 Nov;5(2):141-7. PMID:15489197 doi:10.1016/j.femsyr.2004.07.005
- ↑ Wissing S, Ludovico P, Herker E, Buttner S, Engelhardt SM, Decker T, Link A, Proksch A, Rodrigues F, Corte-Real M, Frohlich KU, Manns J, Cande C, Sigrist SJ, Kroemer G, Madeo F. An AIF orthologue regulates apoptosis in yeast. J Cell Biol. 2004 Sep 27;166(7):969-74. Epub 2004 Sep 20. PMID:15381687 doi:10.1083/jcb.200404138
- ↑ Herker E, Jungwirth H, Lehmann KA, Maldener C, Frohlich KU, Wissing S, Buttner S, Fehr M, Sigrist S, Madeo F. Chronological aging leads to apoptosis in yeast. J Cell Biol. 2004 Feb 16;164(4):501-7. PMID:14970189 doi:10.1083/jcb.200310014
- ↑ Wadskog I, Maldener C, Proksch A, Madeo F, Adler L. Yeast lacking the SRO7/SOP1-encoded tumor suppressor homologue show increased susceptibility to apoptosis-like cell death on exposure to NaCl stress. Mol Biol Cell. 2004 Mar;15(3):1436-44. Epub 2004 Jan 12. PMID:14718573 doi:10.1091/mbc.E03-02-0114
- ↑ Mazzoni C, Herker E, Palermo V, Jungwirth H, Eisenberg T, Madeo F, Falcone C. Yeast caspase 1 links messenger RNA stability to apoptosis in yeast. EMBO Rep. 2005 Nov;6(11):1076-81. Epub 2005 Sep 9. PMID:16170310 doi:10.1038/sj.embor.7400514
- ↑ Reiter J, Herker E, Madeo F, Schmitt MJ. Viral killer toxins induce caspase-mediated apoptosis in yeast. J Cell Biol. 2005 Jan 31;168(3):353-8. Epub 2005 Jan 24. PMID:15668299 doi:10.1083/jcb.200408071
- ↑ Vachova L, Palkova Z. Physiological regulation of yeast cell death in multicellular colonies is triggered by ammonia. J Cell Biol. 2005 Jun 6;169(5):711-7. PMID:15939758 doi:10.1083/jcb.200410064
- ↑ Weinberger M, Ramachandran L, Feng L, Sharma K, Sun X, Marchetti M, Huberman JA, Burhans WC. Apoptosis in budding yeast caused by defects in initiation of DNA replication. J Cell Sci. 2005 Aug 1;118(Pt 15):3543-53. PMID:16079294 doi:10.1242/jcs.02477
- ↑ Khan MA, Chock PB, Stadtman ER. Knockout of caspase-like gene, YCA1, abrogates apoptosis and elevates oxidized proteins in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 2005 Nov 29;102(48):17326-31. Epub 2005 Nov 21. PMID:16301538 doi:10.1073/pnas.0508120102
- ↑ Lee RE, Brunette S, Puente LG, Megeney LA. Metacaspase Yca1 is required for clearance of insoluble protein aggregates. Proc Natl Acad Sci U S A. 2010 Jul 27;107(30):13348-53. doi:, 10.1073/pnas.1006610107. Epub 2010 Jul 12. PMID:20624963 doi:10.1073/pnas.1006610107
- ↑ Wong AH, Yan C, Shi Y. Crystal structure of the yeast metacaspase Yca1. J Biol Chem. 2012 Aug 24;287(35):29251-9. doi: 10.1074/jbc.M112.381806. Epub 2012, Jul 2. PMID:22761449 doi:https://dx.doi.org/10.1074/jbc.M112.381806
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