权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

ENYZMES AFFECTING THE ACCUMULATION OF ALTERED PROTEINS

影响改变蛋白质积累的酶

基本信息

批准号：
6631470
负责人：
STEVEN G CLARKE
金额：
$ 22.59万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-06-15 至 2005-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6631470
关键词：
Arabidopsis Caenorhabditis elegans Escherichia coli Saccharomyces cerevisiae aging aspartate enzyme mechanism gene mutation grain methyltransferase protein metabolism

项目摘要

DESCRIPTION: (Adapted from the Application). The manifestations of aging result in part from cells becoming less efficient at self-repair with time. These reactions represent one part of the battle of organisms to maintain the structural integrity of essential macromolecules in the face of the molecules intrinsic instabilities. Defects in these mechanisms may underlie pathologies where the aging process can be accelerated. The objective of this work is to understand how aging organisms prevent the accumulation of covalently altered proteins that can compromise cellular functions. These investigators will characterize the role of the protein L-isoaspartate (D-aspartate) O-methyltransferase that recognizes spontaneously-damaged proteins and catalyzes the initial step of a protein repair reaction. The discovery of this pathway reveals that macromolecular repair may not be just for DNA, but for proteins as well. These investigators propose to ask how the potential accumulation of damaged proteins in aging is reduced by methylation and other pathways in viva. They will utilize model organisms including bacteria, yeast, worms, and plants. Specifically, we will characterize protein damage in the bacterium Escherichia coli. They will study mutant phenotypes of both the methyltransferase pcm gene and the sure gene shown to be present in an operon with pcm. They will also study the role of associated enzymes that are involved in the metabolism of isoaspartyl-containing proteins and peptides, including isoaspartyl dipeptidases. They will analyze mutants of the protein repair methyltransferase in the nematode worm Casnorhabditis elegant. They will ask how the yeast Saccharomyces cerevisiae can avoid the accumulation of proteins containing altered aspartyl residues in spite of the fact that it naturally lacks the methyltransferase. Finally, they will examine the role of the methylation reaction in controlling protein damage in higher plants, including corn and Arabidopsis. These studies will hopefully not only provide a new window to view protein life but may also suggest that the biological aging process may be closely linked to how well cells can keep polypeptides free of spontaneous covalent damage.

描述：（改编自应用程序）。衰老的表现部分原因是随着时间的推移，细胞的自我修复效率越来越低。这些反应代表了生物体为维持自身免疫力而进行的战斗的一部分。基本大分子的结构完整性，内在不稳定性这些机制的缺陷可能是病理的基础可以加速老化过程。这项工作的目标是了解衰老的生物体如何阻止共价改变的会损害细胞功能的蛋白质这些调查人员将表征蛋白质L-异天冬氨酸（D-天冬氨酸）的作用 O-甲基转移酶，识别自发受损的蛋白质，催化蛋白质修复反应的初始步骤。的发现这一途径揭示了大分子修复可能不仅仅是DNA，蛋白质也是如此。这些研究人员提出，在衰老过程中受损蛋白质的积累通过甲基化和其他在viva的路径他们将利用包括细菌在内的模式生物，酵母、蠕虫和植物。具体来说，我们将描述蛋白质损伤在大肠杆菌中。他们将研究甲基转移酶pcm基因和sure基因都显示存在于带有PCM的操纵子。他们还将研究相关酶的作用，参与含异戊酰基蛋白质的代谢，肽，包括异戊酰二肽酶。他们将分析线虫中的蛋白质修复甲基转移酶优雅. 他们会问酿酒酵母如何避免积累的蛋白质含有改变的乙酰基残基，尽管事实上，它天然缺乏甲基转移酶。最后，他们会研究甲基化反应在控制蛋白质损伤中的作用，高等植物，包括玉米和拟南芥。这些研究将有望不仅提供了一个观察蛋白质生命的新窗口，生物老化过程可能与细胞保持无自发共价损伤的多肽。

项目成果

期刊论文数量（27）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Yeast, plants, worms, and flies use a methyltransferase to metabolize age-damaged (R,S)-AdoMet, but what do mammals do?

酵母、植物、蠕虫和苍蝇使用甲基转移酶来代谢因年龄受损的 (R,S)-AdoMet，但哺乳动物会做什么呢？

DOI：
10.1089/rej.2009.0956
发表时间：
2010
期刊：
Rejuvenation research
影响因子：
2.6
作者：
Vinci,ChrisR;Clarke,StevenG
通讯作者：
Clarke,StevenG

Intracellular protein modification associated with altered T cell functions in autoimmunity.

细胞内蛋白质修饰与自身免疫中 T 细胞功能的改变相关。

DOI：
10.4049/jimmunol.177.7.4541
发表时间：
2006
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
0
作者：
Yang,Mei-Ling;Doyle,HesterA;Gee,RenelleJ;Lowenson,JonathanD;Clarke,Steven;Lawson,BrianR;Aswad,DanaW;Mamula,MarkJ
通讯作者：
Mamula,MarkJ

Protein repair methyltransferase from the hyperthermophilic archaeon Pyrococcus furiosus. Unusual methyl-accepting affinity for D-aspartyl and N-succinyl-containing peptides.

来自超嗜热古菌激烈火球菌的蛋白质修复甲基转移酶。