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Initial Amino Acid:Codon Assignments and Strength of Codon:Anticodon Binding
Journal of the American Chemical Society ( IF 15.0 ) Pub Date : 2024-04-27 , DOI: 10.1021/jacs.4c03644
Meng Su 1 , Samuel J. Roberts 1 , John D. Sutherland 1
Affiliation  

The ribosome brings 3′-aminoacyl-tRNA and 3′-peptidyl-tRNAs together to enable peptidyl transfer by binding them in two major ways. First, their anticodon loops are bound to mRNA, itself anchored at the ribosomal subunit interface, by contiguous anticodon:codon pairing augmented by interactions with the decoding center of the small ribosomal subunit. Second, their acceptor stems are bound by the peptidyl transferase center, which aligns the 3′-aminoacyl- and 3′-peptidyl-termini for optimal interaction of the nucleophilic amino group and electrophilic ester carbonyl group. Reasoning that intrinsic codon:anticodon binding might have been a major contributor to bringing tRNA 3′-termini into proximity at an early stage of ribosomal peptide synthesis, we wondered if primordial amino acids might have been assigned to those codons that bind the corresponding anticodon loops most tightly. By measuring the binding of anticodon stem loops to short oligonucleotides, we determined that family-box codon:anticodon pairings are typically tighter than split-box codon:anticodon pairings. Furthermore, we find that two family-box anticodon stem loops can tightly bind a pair of contiguous codons simultaneously, whereas two split-box anticodon stem loops cannot. The amino acids assigned to family boxes correspond to those accessible by what has been termed cyanosulfidic chemistry, supporting the contention that these limited amino acids might have been the first used in primordial coded peptide synthesis.

中文翻译:

初始氨基酸:密码子分配和密码子强度:反密码子结合

核糖体将 3'-氨酰基-tRNA 和 3'-肽基-tRNA 结合在一起,通过两种主要方式结合它们来实现肽基转移。首先,它们的反密码子环与 mRNA 结合,而 mRNA 本身锚定在核糖体亚基界面上,通过与小核糖体亚基解码中心的相互作用增强的连续反密码子:密码子配对。其次,它们的受体茎由肽基转移酶中心结合,该中心将 3'-氨酰基和 3'-肽基末端对齐,以实现亲核氨基和亲电酯羰基的最佳相互作用。推断内在密码子:反密码子结合可能是在核糖体肽合成的早期阶段使 tRNA 3' 末端接近的主要因素,我们想知道原始氨基酸是否可能已被分配给那些结合相应反密码子环的密码子最紧。通过测量反密码子茎环与短寡核苷酸的结合,我们确定家族盒密码子:反密码子配对通常比分裂盒密码子:反密码子配对更紧密。此外,我们发现两个家族盒反密码子茎环可以同时紧密结合一对连续密码子,而两个分裂盒反密码子茎环则不能。分配给家族框的氨基酸对应于那些可通过所谓的氰硫化学获得的氨基酸,支持这样的论点:这些有限的氨基酸可能是最先用于原始编码肽合成的。
更新日期:2024-04-27
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