The human mitochondrial tRNAMet: structure/function relationship of a unique modification in the decoding of unconventional codons.
The human mitochondrial tRNAMet: structure/function relationship of a unique modification in the decoding of unconventional codons.
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DOI：
10.1016/j.jmb.2010.11.042
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发表时间：
2011-02-18
影响因子：
5.6
通讯作者：
Agris PF
中科院分区：
文献类型：
--
作者：
Bilbille Y;Gustilo EM;Harris KA;Jones CN;Lusic H;Kaiser RJ;Delaney MO;Spremulli LL;Deiters A;Agris PF
人线粒体mRNA利用通用AUG和非常规异亮氨酸AUA密码子用于甲硫氨酸。与细胞质中的翻译相反，人类线粒体使用一种tRNA hmtRNAMetCAU来读取核糖体的肽基（P-）和氨酰基（A-）位点处的AUG和AUA密码子。hmtRNAMetCAU具有独特的转录后修饰，5-甲酰基胞苷，在摆动位置34（f5 C34），和胞苷取代在tRNA的典型“U形转弯”的位置33的不变尿苷。通过NMR限制的分子模型确定的tRNA的反密码子茎和环结构域（hmtASLMetCAU）的结构揭示了f5 C34修饰如何促进AUA在P-和A-位点的解码。f5 C34定义了核苷的减少的构象空间，似乎限制了修饰的hmtASLMetCAU的反密码子碱基的构象动力学。hmtASLMetCAU呈现具有U形转角基序的一些特征的“C形转角”构象。用E.大肠杆菌和牛线粒体核糖体的研究表明，f5 C34促进AUA在A位点的结合，并表明该修饰有利地改变了ASL的结合动力学。包括人类在内的许多生物体的线粒体翻译有时以通用异亮氨酸密码子AUU和AUC起始。f5 C34使P位点密码子能够与这些正常的异亮氨酸密码子结合。因此，在线粒体中通用密码子的重新分配中，这一修饰f5 C34的物理化学性质将密码子识别从传统的AUG扩展到非传统的同义密码子AUU和AUC以及AUA。
Human mitochondrial mRNAs utilize the universal AUG and the unconventional isoleucine AUA codons for methionine. In contrast to translation in the cytoplasm, human mitochondria use one tRNA, hmtRNAMetCAU, to read AUG and AUA codons at both the peptidyl- (P-), and aminoacyl-(A-) sites of the ribosome. The hmtRNAMetCAU has a unique post-transcriptional modification, 5-formylcytidine, at the wobble position 34 (f5C34), and a cytidine substituting for the invariant uridine at position 33 of the canonical “U-turn” in tRNAs. The structure of the tRNA's anticodon stem and loop domain (hmtASLMetCAU), determined by NMR restrained molecular modeling, revealed how the f5C34 modification facilitates the decoding of AUA at the P- and A-sites. The f5C34 defined a reduced conformational space for the nucleoside, in what appears to have restricted the conformational dynamics of the anticodon bases of the modified hmtASLMetCAU. The hmtASLMetCAU exhibited a “C-turn” conformation that has some characteristics of the U-turn motif. Codon binding studies with both E. coli and bovine mitochondrial ribosomes revealed that the f5C34 facilitates AUA binding in the A-site and suggested that the modification favorably alters the ASL's binding kinetics. Mitochondrial translation by many organisms including humans sometimes initiates with the universal isoleucine codons AUU and AUC. The f5C34 enabled P-site codon binding to these normally isoleucine codons. Thus, the physicochemical properties of this one modification, f5C34, expand codon recognition from the traditional AUG to the non-traditional, synonymous codons AUU and AUC as well as AUA, in the reassignment of universal codons in the mitochondria.
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影响因子：
14.9
作者：
Jühling F;Mörl M;Hartmann RK;Sprinzl M;Stadler PF;Pütz J
通讯作者：
Pütz J
影响因子：
14.9
作者：
Barraud P;Schmitt E;Mechulam Y;Dardel F;Tisné C
通讯作者：
Tisné C
DOI：
10.1107/s0907444998003254
发表时间：
1998-09-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
--
作者：
Brunger, AT;Adams, PD;Warren, GL
通讯作者：
Warren, GL
影响因子：
2.7
作者：
DELAGLIO, F;GRZESIEK, S;BAX, A
通讯作者：
BAX, A
影响因子：
14.9
作者：
AUJAME, L;FREEMAN, KB
通讯作者：
FREEMAN, KB