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Role of the Processing at Amino-Terminus on the Regulation of Half-life of Protein

氨基末端加工对蛋白质半衰期调节的作用

基本信息

批准号：
63044090
负责人：
TSUNASAWA Susumu
金额：
$ 2.18万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for international Scientific Research
财政年份：
1988
资助国家：
日本
起止时间：
1988 至 1990
项目状态：
已结题

项目摘要

A large part of cellular proteins are in a dynamic state of turnover. Protein breakdown is responsible for essential cellular functions such as the modulation of the levels of key enzymes and regulatory proteins and removal of abnormal proteins. For the half-lives of individual proteins it has been reported that N-terminal amino acid is an important factor.To study for the role of N-terminal amino acid on regulation for breakdown of cellular proteins, we have investigated to elucidate the rules of N-terminal processing observed in newly synthesized proteins by using various iso-1-cytochrome c mutants altered at their N-terminal region as a model system, and to isolate the related enzymes.The results suggest that initiator methionine (Met) is completely removed from penultimate residue having radii of glynation on 1, 29 A or less, and that of those newly, appeared amino acids at least glycine, serine and alanine are acetylated depending on some structural characterization. Furthermore, of the retained N-terminal methionine residues, the proteins having both Met-Asp- and Met-Glu sequences are also acetylated. From these results it has been thus estimated that at least the following three enzymes are conjugated in N-terminal processing of proteins. The first enzyme is a methionine aminopeptidase (MAP), which acts on removal of initiator methionine, and the second and the third are N-acetyltransferases with different specificities as suggested above (NAT1 : for glycine, alanine and serine as the N-terminal amino acid ; nat2 : for methionine followed by acidic residues). The isolation of these three enzymes are now undergoing using saccharomyces cerevisiae as the materials.

大部分细胞蛋白质处于动态更新状态。蛋白质分解负责基本的细胞功能，例如调节关键酶和调节蛋白的水平以及去除异常蛋白。对于单个蛋白质的半衰期，据报道N-末端氨基酸是一个重要的因素，为了研究N-末端氨基酸在调节细胞蛋白质分解中的作用，我们使用在其N-末端区域改变的各种异-1-细胞色素c突变体作为模型系统，研究了在新合成的蛋白质中观察到的N-末端加工的规则，结果表明，起始蛋氨酸（Met）在甘氨酸化半径小于等于1.29的倒数第二个残基上被完全去除，新出现的氨基酸中至少有甘氨酸、丝氨酸和丙氨酸被乙酰化，这取决于某些结构特征。此外，在保留的N-末端甲硫氨酸残基中，具有Met-Asp-和Met-Glu序列的蛋白质也被乙酰化。根据这些结果，由此估计，在蛋白质的N-末端加工中至少结合了以下三种酶。第一种酶是甲硫氨酸氨肽酶（MAP），其作用于起始甲硫氨酸的去除，第二种和第三种是具有如上所述的不同特异性的N-乙酰转移酶（NAT 1：用于甘氨酸、丙氨酸和丝氨酸作为N-末端氨基酸; nat 2：用于甲硫氨酸，随后是酸性残基）。这三种酶的分离目前正在以酿酒酵母为原料进行。