Furukawa K, Mizushima N, Noda T, Ohsumi Y
Department of Cell Biology, National Institute for Basic Biology, Okazaki 444-8585, Japan.
J Biol Chem. 2000 Mar 17;275(11):7462-5. doi: 10.1074/jbc.275.11.7462.
Protein conjugation, such as ubiquitination, is the process by which the C-terminal glycine of a small modifier protein is covalently attached to target protein(s) through sequential reactions with an activating enzyme and conjugating enzymes. Here we report on a novel protein conjugation system in yeast. A newly identified ubiquitin related modifier, Urm1 is a 99-amino acid protein terminated with glycine-glycine. Urm1 is conjugated to target proteins, which requires the C-terminal glycine of Urm1. At the first step of this reaction, Urm1 forms a thioester with a novel E1-like protein, Uba4. Deltaurm1 and Deltauba4 cells showed a temperature-sensitive growth phenotype. Urm1 and Uba4 show similarity to prokaryotic proteins essential for molybdopterin and thiamin biosynthesis, although the Urm1 system is not involved in these pathways. This is the fifth conjugation system in yeast, following ubiquitin, Smt3, Rub1, and Apg12, but it is unique in respect to relation to prokaryotic enzyme systems. This fact may provide an important clue regarding evolution of protein conjugation systems in eukaryotic cells.
蛋白质缀合，如泛素化，是一个小分子修饰蛋白的C末端甘氨酸通过与激活酶和缀合酶的一系列反应共价连接到靶蛋白上的过程。在此，我们报道了酵母中的一种新型蛋白质缀合系统。一种新鉴定的泛素相关修饰物Urm1是一种由99个氨基酸组成的、以甘氨酸-甘氨酸结尾的蛋白质。Urm1与靶蛋白缀合，这需要Urm1的C末端甘氨酸。在该反应的第一步，Urm1与一种新型的类E1蛋白Uba4形成硫酯。Deltaurm1和Deltauba4细胞表现出温度敏感的生长表型。Urm1和Uba4与钼蝶呤和硫胺素生物合成所必需的原核蛋白相似，尽管Urm1系统不参与这些途径。这是继泛素、Smt3、Rub1和Apg12之后酵母中的第五种缀合系统，但就与原核酶系统的关系而言它是独特的。这一事实可能为真核细胞中蛋白质缀合系统的进化提供重要线索。
