Tobias J W, Shrader T E, Rocap G, Varshavsky A
Department of Biology, Massachusetts Institute of Technology, Cambridge 02139.
Science. 1991 Nov 29;254(5036):1374-7. doi: 10.1126/science.1962196.
The N-end rule relates the in vivo half-life of a protein to the identity of its amino-terminal residue. Distinct versions of the N-end rule operate in all eukaryotes examined. It is shown that the bacterium Escherichia coli also has the N-end rule pathway. Amino-terminal arginine, lysine, leucine, phenylalanine, tyrosine, and tryptophan confer 2-minute half-lives on a test protein; the other amino-terminal residues confer greater than 10-hour half-lives on the same protein. Amino-terminal arginine and lysine are secondary destabilizing residues in E. coli because their activity depends on their conjugation to the primary destabilizing residues leucine or phenylalanine by leucine, phenylalanine-transfer RNA-protein transferase. The adenosine triphosphate-dependent protease Clp (Ti) is required for the degradation of N-end rule substrates in E. coli.
N端规则将蛋白质在体内的半衰期与其氨基末端残基的特性联系起来。在所有已检测的真核生物中都存在不同版本的N端规则。研究表明，细菌大肠杆菌也具有N端规则途径。氨基末端的精氨酸、赖氨酸、亮氨酸、苯丙氨酸、酪氨酸和色氨酸赋予一种测试蛋白2分钟的半衰期；其他氨基末端残基则赋予同一蛋白超过10小时的半衰期。在大肠杆菌中，氨基末端的精氨酸和赖氨酸是二级不稳定残基，因为它们的活性取决于通过亮氨酸、苯丙氨酸 - 转运RNA - 蛋白质转移酶与一级不稳定残基亮氨酸或苯丙氨酸的缀合。大肠杆菌中N端规则底物的降解需要依赖三磷酸腺苷的蛋白酶Clp（Ti）。
