Regulation of enzyme localization by polymerization:: Polymer formation by the SAM domain of diacylglycerol kinase δ1
Regulation of enzyme localization by polymerization:: Polymer formation by the SAM domain of diacylglycerol kinase δ1
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DOI：
10.1016/j.str.2007.12.017
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发表时间：
2008-03-01
期刊：
影响因子：
5.7
通讯作者：
Bowie, James U.
中科院分区：
文献类型：
--
作者：
Harada, Bryan T.;Knight, Mary Jane;Bowie, James U.
二酰基甘油激酶（DGK）酶通过改变第二信使二酰基甘油的水平而作为细胞内信号传导的调节剂起作用。和磷脂酸。DGK δ和eta同工酶具有共同的蛋白质-蛋白质相互作用模块，称为无菌α基序（SAM）结构域。在DGK δ中，SAM结构域自缔合抑制DGK δ向质膜的易位。在这里，我们表明，DGK三角洲SAM形成一个聚合物和映射的聚合物界面的可溶性突变体的遗传选择。晶体结构显示DGKSAM通过类似于其他SAM结构域聚合物的头-尾相互作用形成螺旋聚合物。通过聚合物界面突变破坏聚合，将DGK delta组成性定位于质膜。因此，DGK δ的聚合通过将DGK δ隔离在非活性细胞位置来调节酶的活性。通过动态聚合进行调节是信号转导中的一个新兴主题。
The diacylglycerol kinase (DGK) enzymes function as regulators of intracellular signaling by altering the levels of the second messengers, diacylglycerol. and phosphatidic acid. The DGK delta and eta isozymes possess a common protein-protein interaction module known as a sterile alpha-motif (SAM) domain. In DGK delta, SAM domain self-association inhibits the translocation of DGK delta to the plasma membrane. Here we show that DGK delta SAM forms a polymer and map the polymeric interface by a genetic selection for soluble mutants. A crystal structure reveals that DGKSAM forms helical polymers through a head-to-tail interaction similar to other SAM domain polymers. Disrupting polymerization by polymer interface mutations constitutively localizes DGK delta to the plasma membrane. Thus, polymerization of DGK delta regulates the activity of the enzyme by sequestering DGK delta in an inactive cellular location. Regulation by dynamic polymerization is an emerging theme in signal transduction.