泛素

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泛素卡通模型
Molecular surface of ubiquitin.

泛素英语ubiquitin)是一种存在于大多数真核细胞中的小蛋白。它的主要功能是标记需要分解掉的蛋白质,使其被水解。当附有泛素的蛋白质移动到桶状的蛋白酶的时候,蛋白酶就会将该蛋白质水解。泛素也可以标记跨膜蛋白,如受体,将其从细胞膜上除去。

1974年,G.格鲁斯坦第一次从小牛胸腺中提取8.5kd的多肽(胸腺生成素),后来在哺乳类的组织、鱼类昆虫等均有发现。

泛素由76个氨基酸组成,分子量大约8500道尔顿。它在真核生物中具有高度保留性,人类和酵母的泛素有96%的相似性。

人类基因组约有3万个编码基因,蛋白转录后经剪接、修饰,可达几十万种,包括细胞的结构蛋白、激素、酶、转录因子等,有序的调节生命活动。蛋白酶降解,如胰蛋白酶小肠内的食物蛋白消化成小肽、氨基酸,被小肠吸收;细胞内吞作用将外来蛋白吞入细胞,在食物泡内被溶酶体的消化酶吸收,不耗能量。

泛素化[编辑]

泛素化系统

泛素化是一种酶促的、蛋白质翻译后修饰(PTM)过程,其中来自被激活泛素的二甘氨酸模体中末端甘氨酸的羧基与被修饰蛋白中赖氨酸ε氨基相连形成一酰胺键。

将蛋白标记上泛素的过程(泛素化)包括了以下一系列步骤:

  1. 泛素的活化:: Ubiquitin is activated in a two-step reaction by an E1 ubiquitin-activating enzyme in a process requiring ATP as an energy source. The initial step involves production of a ubiquitin-adenylate intermediate. The second step transfers ubiquitin to the E1 活性部位 半胱氨酸 residue, with release of AMP. This step results in a thioester linkage between the C-terminal carboxyl group of ubiquitin and the E1 cysteine sulfhydryl group.
  2. Transfer of ubiquitin from E1 to the 活性部位 cysteine of a 泛素缀合酶 E2 via a 转硫酯化反应. Mammalian genomes contain 30–40 UBCs.
  3. The final step of the ubiquitylation cascade creates an isopeptide bond between a lysine of the target protein and the C-terminal glycine of ubiquitin. In general, this step requires the activity of one of the hundreds of E3 ubiquitin-protein ligases (often termed simply 泛素连接酶). E3 enzymes function as the substrate recognition modules of the system and are capable of interaction with both E2 and substrate.

In the ubiquitination cascade, E1 can bind with dozens of E2s, which can bind with hundreds of E3s in a hierarchical way. Other ubiquitin-like proteins (ULPs) are also modified via the E1–E2–E3 cascade.

E3[编辑]

E3酶具有possess one of two domains:

  • The HECT (Homologous to the E6-AP Carboxyl Terminus) domain
  • The RING (Really Interesting New Gene) domain (or the closely related U-box domain)

Transfer can occur in two ways:

  • Directly from E2, catalysed by RING domain E3s.
  • Via an E3 enzyme, catalysed by HECT domain E3s. In this case, a covalent E3-ubiquitin intermediate is formed before transfer of ubiquitin to the substrate protein.

The anaphase-promoting complex (APC) and the SCF complex (for Skp1-Cullin-F-box protein complex) are two examples of multi-subunit E3s involved in recognition and ubiquitination of specific target proteins for degradation by the proteasome.

2004年,阿龙·切哈诺沃阿夫拉姆·赫什科欧文·罗斯因发现了泛素调节的蛋白质降解过程而获得了诺贝尔化学奖

参考文献[编辑]