鸟氨酸转氨甲酰酶前导肽通过其中间部分结构和净正电荷引导线粒体导入。
The ornithine transcarbamylase leader peptide directs mitochondrial import through both its midportion structure and net positive charge.
作者信息
Horwich A L, Kalousek F, Fenton W A, Furtak K, Pollock R A, Rosenberg L E
出版信息
J Cell Biol. 1987 Aug;105(2):669-77. doi: 10.1083/jcb.105.2.669.
Abstract
The cytoplasmically synthesized precursor of the mitochondrial matrix enzyme, ornithine transcarbamylase (OTC), is targeted to mitochondria by its NH2-terminal leader peptide. We previously established through mutational analysis that the midportion of the OTC leader peptide is functionally required. In this article, we report that study of additional OTC precursors, altered in either a site-directed or random manner, reveals that (a) the midportion, but not the NH2-terminal half, is sufficient by itself to direct import, (b) the functional structure in the midportion is unlikely to be an amphiphilic alpha-helix, (c) the four arginines in the leader peptide contribute collectively to import function by conferring net positive charge, and (d) surprisingly, proteolytic processing of the leader peptide does not require the presence of a specific primary structure at the site of cleavage, in order to produce the mature OTC subunit.
摘要
线粒体基质酶鸟氨酸转氨甲酰酶（OTC）在细胞质中合成的前体，通过其氨基末端前导肽靶向线粒体。我们之前通过突变分析确定OTC前导肽的中部在功能上是必需的。在本文中，我们报告称，对以定点或随机方式改变的其他OTC前体的研究表明：（a）中部而非氨基末端的一半本身就足以指导导入；（b）中部的功能结构不太可能是两亲性α螺旋；（c）前导肽中的四个精氨酸通过赋予净正电荷共同促进导入功能；（d）令人惊讶的是，前导肽的蛋白水解加工在切割位点不需要特定的一级结构存在，就能产生成熟的OTC亚基。
相似文献
1
The ornithine transcarbamylase leader peptide directs mitochondrial import through both its midportion structure and net positive charge.鸟氨酸转氨甲酰酶前导肽通过其中间部分结构和净正电荷引导线粒体导入。
J Cell Biol. 1987 Aug;105(2):669-77. doi: 10.1083/jcb.105.2.669.
2
Import of rat ornithine transcarbamylase precursor into mitochondria: two-step processing of the leader peptide.大鼠鸟氨酸转氨甲酰酶前体导入线粒体：前导肽的两步加工过程。
J Cell Biol. 1987 Dec;105(6 Pt 1):2631-9. doi: 10.1083/jcb.105.6.2631.
3
Targeting of pre-ornithine transcarbamylase to mitochondria: definition of critical regions and residues in the leader peptide.鸟氨酸转氨甲酰酶前体靶向线粒体：前导肽中关键区域和残基的定义
Cell. 1986 Feb 14;44(3):451-9. doi: 10.1016/0092-8674(86)90466-6.
4
Different structures in the amino-terminal domain of the ornithine transcarbamylase leader peptide are involved in mitochondrial import and carboxyl-terminal cleavage.鸟氨酸转氨甲酰酶前导肽氨基末端结构域中的不同结构参与线粒体导入和羧基末端切割。
Proc Natl Acad Sci U S A. 1988 Dec;85(23):8905-9. doi: 10.1073/pnas.85.23.8905.
5
Arginine in the leader peptide is required for both import and proteolytic cleavage of a mitochondrial precursor.前导肽中的精氨酸对于线粒体前体的导入和蛋白水解切割都是必需的。
Proc Natl Acad Sci U S A. 1985 Aug;82(15):4930-3. doi: 10.1073/pnas.82.15.4930.
6
Mitochondrial import and processing of mutant human ornithine transcarbamylase precursors in cultured cells.培养细胞中线粒体对突变型人鸟氨酸转氨甲酰酶前体的导入与加工
Mol Cell Biol. 1988 Dec;8(12):5150-8. doi: 10.1128/mcb.8.12.5150-5158.1988.
7
Structure and expression of a complementary DNA for the nuclear coded precursor of human mitochondrial ornithine transcarbamylase.人线粒体鸟氨酸转氨甲酰酶核编码前体的互补DNA的结构与表达
Science. 1984 Jun 8;224(4653):1068-74. doi: 10.1126/science.6372096.
8
Mitochondrial import of rat pre-ornithine transcarbamylase: accurate processing of the precursor form is not required for uptake into mitochondria, nor assembly into catalytically active enzyme.大鼠鸟氨酸氨基甲酰转移酶前体的线粒体导入：前体形式的精确加工对于导入线粒体以及组装成具有催化活性的酶并非必需。
Protein Eng. 1988 Oct;2(4):297-300. doi: 10.1093/protein/2.4.297.
9
Differences in the human and mouse amino-terminal leader peptides of ornithine transcarbamylase affect mitochondrial import and efficacy of adenoviral vectors.鸟氨酸转氨甲酰酶的人类和小鼠氨基末端前导肽的差异影响线粒体导入及腺病毒载体的功效。
Hum Gene Ther. 2001 Jun 10;12(9):1035-46. doi: 10.1089/104303401750214267.
10
Expression of amplified DNA sequences for ornithine transcarbamylase in HeLa cells: arginine residues may be required for mitochondrial import of enzyme precursor.鸟氨酸转氨甲酰酶的扩增DNA序列在HeLa细胞中的表达：酶前体的线粒体导入可能需要精氨酸残基。
J Cell Biol. 1985 May;100(5):1515-21. doi: 10.1083/jcb.100.5.1515.
引用本文的文献
1
Engineered mitochondria exert potent antitumor immunity as a cancer vaccine platform.工程化线粒体作为癌症疫苗平台发挥强大的抗肿瘤免疫作用。
Cell Mol Immunol. 2024 Nov;21(11):1251-1265. doi: 10.1038/s41423-024-01203-4. Epub 2024 Aug 20.
2
Import of a major mitochondrial enzyme depends on synergy between two distinct helices of its presequence.一种主要线粒体酶的导入取决于其前导序列中两个不同螺旋之间的协同作用。
Biochem J. 2016 Sep 15;473(18):2813-29. doi: 10.1042/BCJ20160535. Epub 2016 Jul 15.
3
A mystery unfolds: Franz-Ulrich Hartl and Arthur L. Horwich win the 2011 Albert Lasker Basic Medical Research Award.一个谜团揭开了：弗朗茨 - 乌尔里希·哈特尔（Franz-Ulrich Hartl）和亚瑟·L·霍维茨（Arthur L. Horwich）荣获2011年阿尔伯特·拉斯克基础医学研究奖。
J Clin Invest. 2011 Oct;121(10):3774-7. doi: 10.1172/jci60889.
4
Molecular cloning and analysis of the nuclear gene MRP-L6 coding for a putative mitochondrial ribosomal protein from Saccharomyces cerevisiae.酿酒酵母中编码一种假定线粒体核糖体蛋白的核基因MRP-L6的分子克隆与分析。
Curr Genet. 1993 Jul-Aug;24(1-2):136-40. doi: 10.1007/BF00324677.
5
Peptide design in machina: development of artificial mitochondrial protein precursor cleavage sites by simulated molecular evolution.机器中的肽设计：通过模拟分子进化开发人工线粒体蛋白前体切割位点
Biophys J. 1995 Feb;68(2):434-47. doi: 10.1016/S0006-3495(95)80205-5.
6
Mitochondrial protein transport--a system in search of mutations.线粒体蛋白质转运——一个寻找突变的系统。
Am J Hum Genet. 1995 Aug;57(2):235-8.
7
Mitochondrial import and processing of mutant human ornithine transcarbamylase precursors in cultured cells.培养细胞中线粒体对突变型人鸟氨酸转氨甲酰酶前体的导入与加工
Mol Cell Biol. 1988 Dec;8(12):5150-8. doi: 10.1128/mcb.8.12.5150-5158.1988.
8
Different structures in the amino-terminal domain of the ornithine transcarbamylase leader peptide are involved in mitochondrial import and carboxyl-terminal cleavage.鸟氨酸转氨甲酰酶前导肽氨基末端结构域中的不同结构参与线粒体导入和羧基末端切割。
Proc Natl Acad Sci U S A. 1988 Dec;85(23):8905-9. doi: 10.1073/pnas.85.23.8905.
9
Sequence and structural requirements of a mitochondrial protein import signal defined by saturation cassette mutagenesis.通过饱和盒式诱变确定的线粒体蛋白质输入信号的序列和结构要求。
Mol Cell Biol. 1989 Mar;9(3):1014-25. doi: 10.1128/mcb.9.3.1014-1025.1989.
10
Scanning detection of mutations in human ornithine transcarbamoylase by chemical mismatch cleavage.通过化学错配切割技术扫描检测人类鸟氨酸转氨甲酰酶中的突变
Proc Natl Acad Sci U S A. 1989 Aug;86(15):5888-92. doi: 10.1073/pnas.86.15.5888.
本文引用的文献
1
Processing of pre-ornithine transcarbamylase requires a zinc-dependent protease localized to the mitochondrial matrix.鸟氨酸转氨甲酰酶前体的加工需要一种定位于线粒体基质的锌依赖性蛋白酶。
Biochem Biophys Res Commun. 1982 Mar 15;105(1):1-7. doi: 10.1016/s0006-291x(82)80002-8.
2
Gap misrepair mutagenesis: efficient site-directed induction of transition, transversion, and frameshift mutations in vitro.缺口错配诱变：体外高效定点诱导转换、颠换和移码突变
Proc Natl Acad Sci U S A. 1982 Mar;79(5):1588-92. doi: 10.1073/pnas.79.5.1588.
3
Processing mechanisms in the biosynthesis of proteins.蛋白质生物合成中的加工机制。
Ann N Y Acad Sci. 1980;343:1-16. doi: 10.1111/j.1749-6632.1980.tb47238.x.
4
Patterns of amino acids near signal-sequence cleavage sites.信号序列切割位点附近的氨基酸模式。
Eur J Biochem. 1983 Jun 1;133(1):17-21. doi: 10.1111/j.1432-1033.1983.tb07424.x.
5
Ornithine transcarbamylase in liver mitochondria.肝脏线粒体中的鸟氨酸转氨甲酰酶。
Mol Cell Biochem. 1982 Nov 26;49(2):97-111. doi: 10.1007/BF00242488.
6
Biogenesis of ornithine transcarbamylase in spfash mutant mice: two cytoplasmic precursors, one mitochondrial enzyme.无特定病原体（SPF）ASH突变小鼠中鸟氨酸转氨甲酰酶的生物合成：两种细胞质前体，一种线粒体酶。
Science. 1983 Oct 28;222(4622):426-8. doi: 10.1126/science.6623083.
7
How mitochondria import proteins.线粒体如何导入蛋白质。
Biochim Biophys Acta. 1984 Jan 27;779(1):65-87. doi: 10.1016/0304-4157(84)90004-2.
8
Receptor sites involved in posttranslational transport of apocytochrome c into mitochondria: specificity, affinity, and number of sites.参与脱辅基细胞色素c向线粒体进行翻译后转运的受体位点：特异性、亲和力及位点数量
Proc Natl Acad Sci U S A. 1983 Aug;80(16):4963-7. doi: 10.1073/pnas.80.16.4963.
9
Targeting of pre-ornithine transcarbamylase to mitochondria: definition of critical regions and residues in the leader peptide.鸟氨酸转氨甲酰酶前体靶向线粒体：前导肽中关键区域和残基的定义
Cell. 1986 Feb 14;44(3):451-9. doi: 10.1016/0092-8674(86)90466-6.
10
Protein import into organelles: hierarchical targeting signals.蛋白质导入细胞器：分级靶向信号
Cell. 1986 Aug 1;46(3):321-2. doi: 10.1016/0092-8674(86)90650-1.
Zotero 插件