对于翻译后多糖化酶酶机制的进化分歧
Krzysztof Rogowski1, François Juge, Juliette van Dijk
1CRBM, CNRS, Université Montpellier 2 and 1, Montpellier, France.
Cell
|June 16, 2009
概括
研究人员发现了修改蛋白质的甘氨酸连接酶,揭示了多糖化对于Drosophila的发育和生育至关重要. 一些人体酶可能已经失去了活性,这表明单甘油化足以满足某些功能.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 多糖化是一种翻译后的修改,涉及向蛋白质添加甘氨酸侧链.
- 这种修饰在微管的关键组成部分 - - 管素上尤为普遍.
- 负责多糖化酶的酶及其功能意义仍然不完全理解.
研究的目的:
- 识别和描述负责蛋白质多糖化酶的酶.
- 调查多糖化在体内,特别是模型生物中的功能性作用.
- 为了探索哺乳动物和Drosophila之间的糖酶功能的进化差异.
主要方法:
- 鉴定了一种保存的甘氨酸结合酶家族.
- 酶性测试以确定哺乳动物和多虫糖酶的催化机制.
- 在Drosophila中进行RNA干扰 (RNAi) 以削减糖酶活性.
- 缺乏甘酶的Drosophila的表型分析,包括生育和发育评估.
主要成果:
- 鉴定出一种保存的甘氨酸连接酶家族,通过不同的酶机制催化蛋白质多糖化.
- 哺乳动物甘酶作为两种不同的酶类型 (启动和延伸) 起作用,而多索菲拉甘酶则是双功能.
- 人类延长型甘酶已经失去了酶活性,这表明单甘化可能足以满足某些功能.
- 在Drosophila中,甘酸酶的减少导致了总甘化,男性不孕不育和发育死亡率的减少,突出显示了蛋白质甘化的重要作用.
结论:
- 蛋白质多糖化由一种具有多种酶机制的保存型甘氨酸结合酶家族介导.
- 多糖化对于多种生物过程至关重要,包括精子个性化,轴突膜维护和胚胎发育.
- 糖酶功能的进化分歧表明,在一些物种中,如人类,可能会向单糖化转变.
- 这些发现表明蛋白质糖化在细胞功能中的一般和基本作用.
相关概念视频
Oligosaccharide Assembly
Protein glycosylation starts in the ER lumen and continues in the Golgi apparatus. Glycosyltransferases catalyze the addition of sugar molecules or glycosylation of proteins. Usually, these enzymes add sugars to the hydroxyl groups of selected serine or threonine residues to form O-linked glycans or the amino groups of asparagine residues to form N-linked glycans. Different positions on the same polypeptide chain can contain differently linked glycans.
Multiple sugar molecules that may or may...
Multiple sugar molecules that may or may...
Protein Folding Quality Check in the RER
ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
Protein Modifications in the RER
Modification of secretory and transmembrane proteins entering the rough ER begins in the ER lumen. These modifications aid in protein folding and stabilize the acquired tertiary structure. Protein modifications in the rough ER co-occur at different stages of protein folding.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal sequences.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal sequences.
Protein Glycosylation
Glycosylation, the most common post-translational modification for proteins, serves diverse functions. Adding sugars to proteins makes the proteins more resistant to proteolytic digestion. Glycosylated proteins can act as markers and receptors to promote cell-cell adhesion. Additionally, they have many essential quality control functions in the cell, such as correct protein folding and facilitating transport of misfolded proteins to the cytosol, which can be degraded.
Glycosylation occurs in...
Glycosylation occurs in...
Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.
Protein Complexes with Interchangeable Parts
Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...

