N-terminal acetylation inhibits protein targeting to the endoplasmic reticulum.
N-terminal acetylation inhibits protein targeting to the endoplasmic reticulum.
复制标题
DOI：
10.1371/journal.pbio.1001073
复制
发表时间：
2011-05
期刊：
影响因子：
9.8
通讯作者：
Stirling CJ
中科院分区：
文献类型：
--
作者：
Forte GM;Pool MR;Stirling CJ
氨基末端乙酰化可能是真核生物中最常见的蛋白质修饰，据报道多达 50%–80% 的蛋白质以这种方式改变。在这里，我们报告了对预测的胞浆蛋白 N 端加工与那些注定被分类到分泌途径的蛋白的系统分析。虽然胞浆蛋白明显偏向于加工，但我们发现对分泌蛋白的这种修饰存在相同且相反的偏向。导致其乙酰化的分泌信号序列的突变导致胞质溶胶的错误分选，其方式依赖于N末端加工机制。因此，N-末端乙酰化代表了新生多肽的细胞分选的早期决定步骤，该步骤似乎在多种物种中是保守的。真核细胞包含几个不同的区室，称为细胞器，需要执行特定的功能。这些区室中的蛋白质几乎总是在细胞质中合成，因此需要复杂的分选机制以确保它们输送到适当的细胞器。当然，并非所有蛋白质都需要离开细胞质，因为许多蛋白质仍留在那里执行细胞质功能。众所周知，许多蛋白质在其合成的早期阶段就通过其氨基末端的乙酰化进行修饰。我们发现，细胞质蛋白和内质网 (ER) 等主要细胞器中的蛋白发生这种修饰的可能性之间存在显着差异：虽然细胞质蛋白通常是乙酰化的，但与 ER 结合的蛋白基本上未修饰。此外，当特定的内质网蛋白被设计来诱导其乙酰化时，我们发现它们对内质网的靶向被抑制。我们的数据表明，N 末端乙酰化是真核生物蛋白质分选的主要决定因素。
Amino-terminal acetylation is probably the most common protein modification in eukaryotes with as many as 50%–80% of proteins reportedly altered in this way. Here we report a systematic analysis of the predicted N-terminal processing of cytosolic proteins versus those destined to be sorted to the secretory pathway. While cytosolic proteins were profoundly biased in favour of processing, we found an equal and opposite bias against such modification for secretory proteins. Mutations in secretory signal sequences that led to their acetylation resulted in mis-sorting to the cytosol in a manner that was dependent upon the N-terminal processing machinery. Hence N-terminal acetylation represents an early determining step in the cellular sorting of nascent polypeptides that appears to be conserved across a wide range of species. The eukaryotic cell comprises several distinct compartments, called organelles, required to perform specific functions. The proteins in these compartments are almost always synthesised in the cytoplasm and so require complex sorting mechanisms to ensure their delivery to the appropriate organelle. Of course, not all proteins need to leave the cytoplasm since many remain there to perform cytoplasmic functions. It is well known that many proteins are modified by acetylation of their amino-terminus at a very early stage in their synthesis. We have discovered a profound difference between the likelihood of such a modification on cytoplasmic proteins and on those destined for one of the major organelles, the endoplasmic reticulum (ER): whereas cytoplasmic proteins are typically acetylated, those bound for the ER are largely unmodified. Moreover, when specific ER proteins were engineered to induce their acetylation we found that their targeting to the ER was inhibited. Our data suggest that N-terminal acetylation is a major determinant in protein sorting in eukaryotes.
登录
查看更多内容
影响因子：
3
作者：
Choo KH;Tan TW;Ranganathan S
通讯作者：
Ranganathan S
影响因子：
21.3
作者：
Behnia, R;Panic, B;Munro, S
通讯作者：
Munro, S
影响因子：
64.5
作者：
JOHNSON, LM;BANKAITIS, VA;EMR, SD
通讯作者：
EMR, SD
DOI：
10.1073/pnas.95.26.15183
发表时间：
1998-12-22
影响因子：
11.1
作者：
Griffith, EC;Su, Z;Liu, JO
通讯作者：
Liu, JO
影响因子：
64.5
作者：
JUNGNICKEL, B;RAPOPORT, TA
通讯作者：
RAPOPORT, TA