Activity of the acyl-CoA synthetase ACSL6 isoforms: role of the fatty acid Gate-domains.
Activity of the acyl-CoA synthetase ACSL6 isoforms: role of the fatty acid Gate-domains.
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DOI：
10.1186/1471-2091-11-18
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发表时间：
2010-04-29
期刊：
影响因子：
--
通讯作者：
Kuypers FA
中科院分区：
文献类型：
--
作者：
Soupene E;Dinh NP;Siliakus M;Kuypers FA
脂肪酸被酰基辅酶A合成酶激活是从头脂质合成、脂肪酸催化和生物膜重塑所必需的。人长链酰基辅酶A合成酶成员6（ASCL6）是存在于细胞质膜中的一种形式。影响氨基末端和ATP结合位点附近的替代基序的剪接事件产生ACSL 6的不同亚型。具有不同脂肪酸门结构域基序的同种型具有不同的活性，并且缺乏该结构域的形式，同种型3，显示出不可检测的活性。前40个残基截短的酶以比全长蛋白更快的速率产生酰基辅酶A。门控残基，防止进入的脂肪酸底物，除非一个分子的ATP已经访问的催化位点，被确定为酪氨酸亚型1和苯丙氨酸亚型2的位置319。具有或不具有脂肪酸门结构域的所有同种型以及截短N末端的重组蛋白可以相互作用以形成具有相同或不同同种型的酶复合物。替代脂肪酸门结构域基序是人ACSL 6亚型活性的重要决定因素，其似乎作为同源二聚体酶以及与其他剪接形式复合。这些发现提供的证据表明，这些酶种类的多样性可以产生各种酰基辅酶A合成酶活性，这些活性是产生和修复膜中存在的数百种脂质所必需的。
Activation of fatty acids by acyl-CoA synthetase enzymes is required for de novo lipid synthesis, fatty acid catabolism, and remodeling of biological membranes. Human long-chain acyl-CoA synthetase member 6, ASCL6, is a form present in the plasma membrane of cells. Splicing events affecting the amino-terminus and alternative motifs near the ATP-binding site generate different isoforms of ACSL6. Isoforms with different fatty acid Gate-domain motifs have different activity and the form lacking this domain, isoform 3, showed no detectable activity. Enzymes truncated of the first 40 residues generate acyl-CoAs at a faster rate than the full-length protein. The gating residue, which prevents entry of the fatty acid substrate unless one molecule of ATP has already accessed the catalytic site, was identified as a tyrosine for isoform 1 and a phenylalanine for isoform 2 at position 319. All isoforms, with or without a fatty acid Gate-domain, as well as recombinant protein truncated of the N-terminus, can interact to form enzymatic complexes with identical or different isoforms. The alternative fatty acid Gate-domain motifs are essential determinants for the activity of the human ACSL6 isoforms, which appear to act as homodimeric enzyme as well as in complex with other spliced forms. These findings provide evidence that the diversity of these enzyme species could produce the variety of acyl-CoA synthetase activities that are necessary to generate and repair the hundreds of lipid species present in membranes.
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影响因子：
4.8
作者：
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通讯作者：
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DOI：
10.1016/j.bbrc.2004.11.141
发表时间：
2005-02-04
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