Species-specific activation of Cu/Zn SOD by its CCS copper chaperone in the pathogenic yeast Candida albicans.
Species-specific activation of Cu/Zn SOD by its CCS copper chaperone in the pathogenic yeast Candida albicans.
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DOI：
10.1007/s00775-013-1045-x
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发表时间：
2014-06
影响因子：
3
通讯作者：
Culotta, Valeria C.
中科院分区：
文献类型：
--
作者：
Gleason, Julie E.;Li, Cissy X.;Odeh, Hana M.;Culotta, Valeria C.
白色念珠菌是一种具有重要公共卫生意义的致病酵母菌。白念珠菌的毒力需要含有铜和锌的超氧化物歧化酶(SOD1)，但对其生物学特性了解甚少。为此，在面包酵母中检测了白色念珠菌SOD1的活性，酿酒酵母是一个被证明在无脊椎动物、植物和哺乳动物的铜/锌超氧化物歧化酶研究中卓有成效的真核表达系统。尽管酿酒酵母与白念珠菌SOD1分子有80%的相似性，但白念珠菌SOD1在酿酒酵母中并不活跃。SOD1似乎不能与面包酵母SOD1(CCS1)的铜伴侣相互作用。白念珠菌SOD1在第144位含有一个预测决定对CCS1依赖性的脯氨酸。通过突变这个脯氨酸，白色念珠菌SOD1在面包酵母中获得了活性，并且这种活性不依赖于CCS1。我们在白念珠菌中发现了一个可能的CCS1基因，并在该基因座上产生了杂合性和纯合性基因缺失。CCS1的缺失导致SOD1活性的丧失，这与其作为铜伴侣的作用一致。白念珠菌CCS1也恢复了在面包酵母中表达的白念珠菌SOD1的活性。白念珠菌CCS1能很好地激活来自白色念珠菌的SOD1，但不能激活来自酿酒酵母的SOD1。尽管这两个真菌物种的SOD1和CCS1分子具有高度的同源性，但在CCS-SOD相互作用中存在物种特异性的屏障，这可能反映了致病和非感染性酵母截然不同的生活方式。
Candida albicans is a pathogenic yeast of important public health relevance. Virulence of C. albicans requires a copper and zinc containing superoxide dismutase (SOD1), but the biology of C. albicans SOD1 is poorly understood. To this end, C. albicans SOD1 activation was examined in baker’s yeast (Saccharomyces cerevisiae), a eukaryotic expression system proven fruitful for the study of Cu/Zn SODs from invertebrates, plants and mammals. In spite of the 80% similarity between S. cerevisiae and C. albicans SOD1 molecules, C. albicans SOD1 is not active in S. cerevisiae. The SOD1 appears incapable of productive interactions with the copper chaperone for SOD1 (CCS1) of baker’s yeast. C. albicans SOD1 contains a proline at position 144 predicted to dictate dependence on CCS1. By mutating this proline, C. albicans SOD1 gained activity in baker’s yeast and this activity was independent of CCS1. We identified a putative CCS1 gene in C. albicans and created heterozygous and homozygous gene deletions at this locus. Loss of CCS1 resulted in loss of SOD1 activity, consistent with its role as a copper chaperone. C. albicans CCS1 also restored activity to C. albicans SOD1 expressed in baker’s yeast. C. albicans CCS1 is well adapted for activating its partner SOD1 from C. albicans, but not SOD1 from S. cerevisiae. In spite of the high degree of homology between the SOD1 and CCS1 molecules in these two fungal species, there exists a specie-specific barrier in CCS-SOD interactions which may reflect the vastly different lifestyles of the pathogenic versus non-infectious yeast.
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