β-氨基酸降低了三元复合体的稳定性,并改变了翻译延长机制
F Aaron Cruz-Navarrete1,2, Wezley C Griffin1,2, Yuk-Cheung Chan3
1Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, United States.
ACS central science
|July 1, 2024
概括
非自然氨基酸 (nnAAs) 通过破坏关键的三元复合体,可以阻碍蛋白质合成. 这项研究揭示了特定的nnAA异构体如何阻碍核糖体功能和转位,限制它们的治疗潜力.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 合成生物学 合成生物学
背景情况:
- 使用非天然氨基酸 (nnAAs) 的模板蛋白质合成为治疗药物和材料提供了扩大的化学多样性.
- 目前在nnAA结合中的局限性需要对蛋白质合成机制有更深入的了解.
研究的目的:
- 研究nNAA对三元复合体的形成和核糖体利用的影响,这是一个关键的延长基质.
- 阐明不同nnAA异构体如何影响三元复合体稳定性和核糖体处理.
主要方法:
- 采用了集体和单分子光共振能量转移 (FRET) 测量.
- 分析三元复合体的形成,稳定性和与各种氨酸 (Phe) 异构体的核糖体利用情况.
主要成果:
- (R) - 和 (S) -β2-Phe异构体废除了三元复合物的形成.
- (R) - 和 (S) -β3-Phe异构体显著降低了三元复合体的稳定性,并且被核糖体低效地利用.
- (R) -β3-Phe在解码后的转位中也出现了缺陷.
结论:
- 非自然氨基酸可以阻碍多个阶段的蛋白质合成,包括三元复合体形成和核糖体转位.
- 三元复合体形成的效率和稳定性是必须解决的关键瓶,以便在蛋白质合成中成功地纳入nnAA.
相关概念视频
Improving Translational Accuracy
10.0K
Base complementarity between the three base pairs of mRNA codon and the tRNA anticodon is not a failsafe mechanism. Inaccuracies can range from a single mismatch to no correct base pairing at all. The free energy difference between the correct and nearly correct base pairs can be as small as 3 kcal/ mol. With complementarity being the only proofreading step, the estimated error frequency would be one wrong amino acid in every 100 amino acids incorporated. However, error frequencies observed in...
10.0K
Protein Organization
137.3K
Overview
137.3K
Transcription Attenuation in Prokaryotes
15.2K
Transcriptional attenuation occurs when RNA transcription is prematurely terminated due to the formation of a terminator mRNA hairpin structure. Bacteria use these hairpins to regulate the transcription process and control the synthesis of several amino acids including histidine, lysine, threonine, and phenylalanine. Transcription attenuation takes place in the non-coding regions of mRNA.
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
15.2K
tRNA Activation
19.2K
Aminoacyl-tRNA synthetases are present in both eukaryotes and bacteria. Though eukaryotes have 20 different aminoacyl-tRNA synthetases to couple to 20 amino acids, many bacteria do not have genes for all of these aminoacyl-tRNA synthetases. Despite this, they still use all 20 amino acids to synthesize their proteins. For instance, some bacteria do not have the gene encoding the enzyme that couples glutamine with its partner tRNA. In these organisms, one enzyme adds glutamic acid to all of the...
19.2K
Termination of Translation
25.3K
The large ribosomal subunit has several important structures essential to translation. These include the peptidyl transferase center (PTC) - which is the site where the peptide bond is formed - and a large, internal, water-filled tube through which the nascent polypeptide moves. This latter structure is called the Peptide Exit Tunnel, and it begins at the PTC and spans the body of the large ribosomal subunit. During translation, as the nascent polypeptide chain is synthesized, it passes through...
25.3K
RNA Structure
4.8K
The basic structure of RNA consists of a string of ribonucleotides attached by phosphodiester bonds. Although most RNA is single-stranded, it can form complex secondary and tertiary structures. Such structures play essential roles in the regulation of transcription and translation.
Different Types of RNA Have the Same Basic Structure
There are three main types of ribonucleic acid (RNA) involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). All three...
Different Types of RNA Have the Same Basic Structure
There are three main types of ribonucleic acid (RNA) involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). All three...
4.8K


