A six-membrane-spanning topology for yeast and arabidopsis Tsc13p, the enoyl reductases of the microsomal fatty acid elongating system
A six-membrane-spanning topology for yeast and arabidopsis Tsc13p, the enoyl reductases of the microsomal fatty acid elongating system
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DOI：
10.1074/jbc.m701774200
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发表时间：
2007-06-29
影响因子：
4.8
通讯作者：
Dunn, Teresa M.
中科院分区：
文献类型：
--
作者：
Paul, Shilpi;Gable, Kenneth;Dunn, Teresa M.
超长链脂肪酸是必需脂肪的重要组成部分，最明显的是神经鞘脂脂。这些细长的脂肪酸是由一系列酶合成的，这些酶在内质网膜内组成一个复合体。尽管最近已经确定了延伸酶复合体的几个组成部分，但对于这些蛋白质在膜内是如何组织的，或者它们在脂肪酸伸长过程中如何相互作用，人们知之甚少。在本研究中，我们研究了延伸酶系统中的烯醇基还原酶Tsc13p的拓扑结构。Tsc13p的N端和C端位于细胞质中，通过在不同位置插入糖基化和因子Xa裂解位点，确定了6个可能的跨膜结构域。包括第一跨膜片段的N-末端结构域包含靶向内质网膜的足够信息。对拟南芥Tsc13p蛋白的研究发现了类似的拓扑结构。Tsc13p蛋白的高度保守的结构域可能对酶的活性很重要，位于内质网的胞浆表面，可能部分嵌入膜中。
The very long chain fatty acids are crucial building blocks of essential lipids, most notably the sphingolipids. These elongated fatty acids are synthesized by a system of enzymes that are organized in a complex within the endoplasmic reticulum membrane. Although several of the components of the elongase complex have recently been identified, little is known about how these proteins are organized within the membrane or about how they interact with one another during fatty acid elongation. In this study the topology of Tsc13p, the enoyl reductase of the elongase system, was investigated. The N and C termini of Tsc13p reside in the cytoplasm, and six putative membrane-spanning domains were identified by insertion of glycosylation and factor Xa cleavage sites at various positions. The N-terminal domain including the first membrane-spanning segment contains sufficient information for targeting to the endoplasmic reticulum membrane. Studies of the Arabidopsis Tsc13p protein revealed a similar topology. Highly conserved domains of the Tsc13p proteins that are likely to be important for enzymatic activity lie on the cytosolic face of the endoplasmic reticulum, possibly partially embedded within the membrane.