Pestova T V, Lomakin I B, Lee J H, Choi S K, Dever T E, Hellen C U
Department of Microbiology and Immunology, State University of New York Health Science Center at Brooklyn, 11203, USA.
Nature. 2000 Jan 20;403(6767):332-5. doi: 10.1038/35002118.
Initiation of eukaryotic protein synthesis begins with the ribosome separated into its 40S and 60S subunits. The 40S subunit first binds eukaryotic initiation factor (eIF) 3 and an eIF2-GTP-initiator transfer RNA ternary complex. The resulting complex requires eIF1, eIF1A, eIF4A, eIF4B and eIF4F to bind to a messenger RNA and to scan to the initiation codon. eIF5 stimulates hydrolysis of eIF2-bound GTP and eIF2 is released from the 48S complex formed at the initiation codon before it is joined by a 60S subunit to form an active 80S ribosome. Here we show that hydrolysis of eIF2-bound GTP induced by eIF5 in 48S complexes is necessary but not sufficient for the subunits to join. A second factor termed eIF5B (relative molecular mass 175,000) is essential for this process. It is a homologue of the prokaryotic initiation factor IF2 (re and, like it, mediates joining of subunits and has a ribosome-dependent GTPase activity that is essential for its function.
真核生物蛋白质合成的起始过程始于核糖体分离为40S和60S亚基。40S亚基首先结合真核生物起始因子（eIF）3和eIF2 - GTP - 起始转运RNA三元复合物。形成的复合物需要eIF1、eIF1A、eIF4A、eIF4B和eIF4F才能与信使RNA结合并扫描至起始密码子。eIF5刺激与eIF2结合的GTP水解，并且在60S亚基加入形成活性80S核糖体之前，eIF2从在起始密码子处形成的48S复合物中释放出来。我们在此表明，eIF5在48S复合物中诱导的与eIF2结合的GTP水解对于亚基的结合是必要的，但并不充分。另一个称为eIF5B（相对分子质量175,000）的因子对于此过程至关重要。它是原核生物起始因子IF2的同源物，并且与IF2一样，介导亚基的结合，并且具有对其功能至关重要的核糖体依赖性GTP酶活性。
