The physical state of lipid substrates provides transacylation specificity for tafazzin.

The physical state of lipid substrates provides transacylation specificity for tafazzin.
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DOI:
10.1038/nchembio.1064
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发表时间:
2012-10
影响因子:
14.8
通讯作者:
Epand, Richard M.
Epand, Richard M.
中科院分区:
生物学1区
文献类型:
--
作者:
Schlame, Michael;Acehan, Devrim;Berno, Bob;Xu, Yang;Valvo, Salvatore;Ren, Mindong;Stokes, David L.;Epand, Richard M.

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心磷脂是一种线粒体磷脂,具有特征性酰基链组成,其取决于tafazzin(一种磷脂-溶血磷脂转酰酶)的功能,尽管该酶本身缺乏酰基特异性。我们孵育分离的tafazzin与各种混合物的磷脂和溶血磷脂,其特征在于脂质相的31 P-NMR,并测量新形成的分子种类质谱。仅在非双层脂质聚集体中观察到显著的转酰化,并且底物特异性对脂质相高度敏感。特别是,四氢萘油酰基-心磷脂,一种原型分子物种,仅在有利于倒六方相的条件下形成。在分离的线粒体中,<1%的脂质参与转酰化,表明tafazzin的作用仅限于特权脂质结构域。我们提出,tafazzin反应与非双层型脂质结构域发生在弯曲或半融合的膜区,和酰基特异性是由这些结构域的包装性能。
Cardiolipin is a mitochondrial phospholipid with a characteristic acyl chain composition that depends on the function of tafazzin, a phospholipid-lysophospholipid transacylase, although the enzyme itself lacks acyl specificity. We incubated isolated tafazzin with various mixtures of phospholipids and lysophospholipids, characterized the lipid phase by 31P-NMR, and measured newly formed molecular species by mass spectrometry. Significant transacylation was observed only in non-bilayer lipid aggregates and the substrate specificity was highly sensitive to the lipid phase. In particular, tetralinoleoyl-cardiolipin, a prototype molecular species, formed only under conditions that favor the inverted hexagonal phase. In isolated mitochondria, <1 percent of lipids participated in transacylations, suggesting that the action of tafazzin is limited to privileged lipid domains. We propose that tafazzin reacts with non-bilayer type lipid domains that occur in curved or hemifused membrane zones, and that acyl specificity is driven by the packing properties of these domains.
DOI: 10.1074/jbc.m110.171439
发表时间: 2011-01-14
影响因子: 4.8
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发表时间: 2012-07-01
影响因子: 3.4
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