ROLE OF THE A-AMINO GROUP OF PROTEIN IN UBIQUITIN-MEDIATED PROTEIN BREAKDOWN
ROLE OF THE A-AMINO GROUP OF PROTEIN IN UBIQUITIN-MEDIATED PROTEIN BREAKDOWN
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DOI：
10.1073/pnas.81.22.7021
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发表时间：
1984-01-01
期刊：
影响因子：
--
通讯作者：
ROSE, IA
中科院分区：
文献类型：
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作者：
HERSHKO, A;HELLER, H;ROSE, IA
先前的研究表明，泛素与 NH2 蛋白质基团的结合是蛋白质分解所必需的。球蛋白和溶菌酶的NH2-末端α-NH2基团的选择性修饰防止它们被来自[兔]网织红细胞的泛素蛋白水解系统降解。通常以多个形式出现的赖氨酸残基的ε-NH2基团的泛素缀合也在α-NH2封闭的蛋白质中受到抑制。天然存在的 N.α-乙酰化蛋白质不会被泛素系统以显着的速率降解，而来自其他物种的非乙酰化对应物是良好的底物。这表明细胞蛋白质 N.α-乙酰化的功能之一是防止其被泛素系统降解。 α-NH2封闭的蛋白质可以通过引入聚丙氨酸侧链并入α-NH2基团来增强其作为降解底物的活性。大多数ε-NH2基团被封闭但α-NH2基团游离的蛋白质被泛素系统降解，但降解速率降低。蛋白质的游离 NH2 末端的暴露可能是降解所必需的，并且可能引发用于降解的泛素缀合物的形成。
Previous studies suggest the the conjugation of ubiquitin to NH2 groups of proteins is required for protein breakdown. The selective modification of NH2-terminal .alpha.-NH2 groups of globin and lysozyme prevents their degradation by the ubiquitin proteolytic system from [rabbit] reticulocytes. The conjugation by ubiquitin of .epsilon.-NH2 groups of lysine residues, usually seen in multiples, was also inhibited in .alpha.-NH2-blocked proteins. Naturally occurring N.alpha.-acetylated proteins are not degraded by the ubiquitin system at a significant rate, while their nonacetylated counterparts from other species are good substrates. This suggests that one function of N.alpha.-acetylation of cellular proteins is to prevent their degradation by the ubiquitin system. .alpha.-NH2-blocked proteins can have their activity as substrates for degradation increased by incorporation of .alpha.-NH2 groups through the introduction of polyalanine side chains. Proteins in which most .epsilon.-NH2 groups are blocked but the .alpha.-NH2 group is free are degraded by the ubiquitin system, but at a reduced rate. The exposure of a free NH2 terminus of proteins may be required for degradation and probably initiates the formation of ubiquitin conjugates committed for degradation.