リボソームペプチジルトランスファーゼは,推定的触媒核酸の変異に耐えることができる
N Polacek1, M Gaynor, A Yassin
1Center for Pharmaceutical Biotechnology (MC 870), University of Illinois, Chicago, Illinois 60607, USA.
Nature
|May 25, 2001
まとめ
タンパク質合成は,リボソーム内のペプチド結合形成に依存しています. この研究では,重要なRNA残基の変異がペプチジルトランスファーゼの活性に大きく影響しないことが判明し,リボソームが反応を触媒化するのではなく,主に基板を配置することを示唆しました.
科学分野:
- 分子生物学は分子生物学である.
- バイオケミストリー バイオケミストリー
- 構造生物学 構造生物学とは
背景:
- ペプチド結合の形成は,リボソームのペプチジルトランスファーゼセンターで発生するタンパク質合成の中心です.
- 50Sリボソームサブユニットの活性部位にはタンパク質が欠け,RNAの触媒的役割 (リボ酵素) を示す.
- 23SリボソームRNAにおけるアデニン残基A2451は,重要な触媒残基として提案された.
研究 の 目的:
- ペプチド結合形成のリボソームRNA (rRNA) 触媒におけるA2451およびG2447の役割を調査する.
- 特定のrRNAヌクレオチドがペプチジルトランスファーゼ活性に不可欠であるという仮説を検証する.
主な方法:
- 23S rRNA.で突然変異を生じさせるためのインビトロ遺伝学.
- 変異したリボソームサブユニットにおけるペプチジルトランスファーゼ活性を測定するアッセイ.
- エシェリキヤ大腸菌からの大きなリボソームサブユニットの分析.
主要な成果:
- A2451の変異は消滅しなかったが,重要なペプチジルトランスファーゼ活性を維持した.
- G2447の変異は,また,実質的なトランスペプチダーション活性を示した.
- これらの推定的触媒残留物の変化は,ペプチド結合形成率に重大な影響を及ぼさなかった.
結論:
- リボソームは,化学的触媒ではなく,主に基板の位置づけを通じてトランスペプチデーションを促進するようです.
- rRNAにおけるA2451の提案された触媒的役割は,これまで考えられていたよりも批判的ではないかもしれない.
- タンパク質合成におけるリボソームRNAの機能は,直接的な化学的触媒よりも構造的組織に依存する可能性がある.
さらに関連する動画
09:04Studying Ribonucleotide Incorporation: Strand-specific Detection of Ribonucleotides in the Yeast Genome and Measuring Ribonucleotide-induced Mutagenesis
Published on: July 26, 2018
06:18Measurement of Specific Mycobacterial Mistranslation Rates with Gain-of-function Reporter Systems
Published on: April 26, 2019
関連する概念動画
Mismatch Repair
Overview
Translesion DNA Polymerases
Translesion (TLS) polymerases rescue stalled DNA polymerases at sites of damaged bases by replacing the replicative polymerase and installing a nucleotide across the damaged site. Doing so, TLS allows additional time for the cell to repair the damage before resuming regular DNA replication.
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
Transfer RNA Synthesis
One of the unique features of tRNA is the presence of modified bases. In some tRNAs, modified bases account for nearly 20% of the total bases in the molecule. Altogether, these unusual bases protect the tRNA from enzymatic degradation by RNases.
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
Improving Translational Accuracy
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...
Mismatch Repair
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
Mutations in Microorganisms
Mutations are heritable changes in an organism’s genome involving alterations in the base sequence of DNA or RNA. These changes can influence cellular processes and phenotypic traits, potentially transforming the unaltered wild type into a mutant form. Such changes, termed forward mutations, are pivotal in shaping the genetic diversity of organisms.RNA viruses exhibit the highest mutation rates due to the absence of robust proofreading mechanisms during genome replication. In contrast,...
