Regulation of glycoprotein biosynthesis by formation of specific glycosyltransferase complexes.
Regulation of glycoprotein biosynthesis by formation of specific glycosyltransferase complexes.
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通过形成特定的糖基转移酶复合物来调节糖蛋白生物合成。
DOI：
10.1073/pnas.78.7.4021
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发表时间：
1981
影响因子：
11.1
通讯作者：
Ivatt,RJ
中科院分区：
文献类型：
--
作者：
Ivatt,RJ
真核生物表面同时表达蛋白质连接寡糖的复杂阵列，并且在分化和肿瘤转化过程中，这些阵列会发生变化。与蛋白质天冬酰胺残基连接的寡糖是一个复杂的结构家族，它是由一个共同的前体寡糖通过竞争的生物合成途径网络衍生而来的。构成这些生物合成途径的糖基化反应通常具有共同的中间体，这就要求在超分子水平上调节竞争性糖基转移酶之间的竞争。研究了两种顺序的糖基转移酶，它们一起将n -乙酰乳胺添加到糖蛋白中，揭示了它们形成特定复合物的能力。通过研究这些顺序酶进行的偶联反应来评估复合物形成的功能后果。膜酶很容易被预先形成的脂质体吸附，并且它们在脂质体吸附后的相互作用能力允许直接研究这些顺序酶在共同吸附到同一脂质体或吸附到分离的脂质体时所进行的作用，这表明内源性产生的中间体比外源性添加的糖蛋白更优先使用。这促进了中间糖基化糖蛋白在复合物内的通过，导致序列酶的紧密耦合。序列糖基转移酶形成这种复合物被认为是糖蛋白合成过程中控制潜在竞争的糖基化序列之间竞争的一种机制。不同条件下不同特异性复合物的形成为发育过程中调节细胞表面糖蛋白的合成提供了一种灵活的机制。
Eukaryotic surfaces simultaneously express a complex array of protein-linked oligosaccharides and, during differentiation and on neoplastic transformation, these arrays change. The oligosaccharides linked to asparagine residues of proteins are a complex family of structures that are derived from a common precursor oligosaccharide by a network of competing biosynthetic pathways. The glycosylation reactions that make up these biosynthetic pathways often share common intermediates, requiring the competition between rival glycosyltransferases to be regulated at the supramolecular level. Investigation of two sequential glycosyltransferases that together add N-acetyllactosamine to glycoproteins has revealed their ability to form specific complexes. The functional consequences of complex formation were assessed by investigating the coupled reaction carried out by these sequential enzymes. The membrane enzymes are readily adsorbed by preformed liposomes, and their ability to interact after liposome adsorption has allowed direct investigation of the action carried out by these sequential enzymes when they are coadsorbed to the same liposome or adsorbed to separate liposomes shows the preferential use of endogenously generated intermediate over exogenously added glycoproteins. This facilitated passage of the intermediate glycosylated glycoprotein within the complex results in a tight coupling of the sequential enzymes. The formation of such complexes by sequential glycosyltransferases is proposed as a mechanism for controlling the competition between potentially rival glycosylation sequences during glycoprotein synthesis. The formation of different specific complexes under different conditions provides a flexible mechanism for regulating the synthesis of cell surface glycoproteins during development.