人类真核释放因子eRF1的晶体结构——终止密码子识别及肽基-tRNA水解机制

The crystal structure of human eukaryotic release factor eRF1--mechanism of stop codon recognition and peptidyl-tRNA hydrolysis.

作者信息

Song H, Mugnier P, Das A K, Webb H M, Evans D R, Tuite M F, Hemmings B A, Barford D

机构信息

Section of Structural Biology, Institute of Cancer Research, London, United Kingdom.

出版信息

Cell. 2000 Feb 4;100(3):311-21. doi: 10.1016/s0092-8674(00)80667-4.

DOI:10.1016/s0092-8674(00)80667-4

PMID:10676813

Abstract

The release factor eRF1 terminates protein biosynthesis by recognizing stop codons at the A site of the ribosome and stimulating peptidyl-tRNA bond hydrolysis at the peptidyl transferase center. The crystal structure of human eRF1 to 2.8 A resolution, combined with mutagenesis analyses of the universal GGQ motif, reveals the molecular mechanism of release factor activity. The overall shape and dimensions of eRF1 resemble a tRNA molecule with domains 1, 2, and 3 of eRF1 corresponding to the anticodon loop, aminoacyl acceptor stem, and T stem of a tRNA molecule, respectively. The position of the essential GGQ motif at an exposed tip of domain 2 suggests that the Gln residue coordinates a water molecule to mediate the hydrolytic activity at the peptidyl transferase center. A conserved groove on domain 1, 80 A from the GGQ motif, is proposed to form the codon recognition site.

摘要

释放因子eRF1通过识别核糖体A位点的终止密码子并刺激肽基转移酶中心的肽基 - tRNA键水解来终止蛋白质生物合成。人eRF1的晶体结构分辨率达到2.8 Å，结合对通用GGQ基序的诱变分析，揭示了释放因子活性的分子机制。eRF1的整体形状和尺寸类似于tRNA分子，eRF1的结构域1、2和3分别对应于tRNA分子的反密码子环、氨酰基受体茎和T茎。必需的GGQ基序位于结构域2的暴露末端，这表明Gln残基协调一个水分子以介导肽基转移酶中心的水解活性。在距离GGQ基序80 Å的结构域1上有一个保守的凹槽，被认为形成了密码子识别位点。