相关实验视频

Updated: May 15, 2025

Dual DNA Rulers to Study the Mechanism of Ribosome Translocation with Single-Nucleotide Resolution

Dual DNA Rulers to Study the Mechanism of Ribosome Translocation with Single-Nucleotide Resolution

Published on: July 8, 2019

分子洞察到人类基体的整体结构的分子洞察

Ji Huang¹, Liang Tong²

¹Department of Biological Sciences, Columbia University, New York, NY, USA.

Nature communications

|April 8, 2025

概括

这项研究揭示了人类核糖体的结构组织,核糖体生物生成中必不可少的蛋白质复合体. 冷-EM结构显示了像LAS1L-NOL9这样的催化模块如何与核心支架结合,由突变发生证实.

科学领域:

分子生物学分子生物学
结构生物学结构生物学
细胞生物学细胞生物学

背景情况:

瑞克索姆是一种保存的蛋白质复合体,对核糖体生物发生和Polycomb目标基因沉默至关重要.
关键的人类子单元包括PELP1,WDR18,TEX10,LAS1L (内分核酶) 和NOL9 (RNA 5'激酶).

研究的目的:

通过冷电子显微镜 (cryo-EM) 测定人体素子组合的结构.
阐明人体基体核心支架和催化模块招募的组装和组织.
通过突变发生学来研究特定子单元相互作用的功能作用.

主要方法:

电子显微镜 (cryo-EM) 用于结构的确定.
变异性研究以验证结构发现并评估蛋白质与蛋白质相互作用.

主要成果:

提供了PELP1-WDR18-TEX10和LAS1L-NOL9复合体的冷EM结构,以及PELP1-WDR18-LAS1L.L的较低分辨率模型.
揭示了核心支架组织 (PELP1-WDR18-TEX10-LAS1L) 和LAS1L-NOL9催化模块的招募机制.
确定了特定的相互作用点:TEX10-WDR18接触点和WDR18C端螺旋与LAS1L的相互作用.
突变发生证实了WDR18-TEX10相互作用区域和WDR18 C终端螺旋对结合的重要性.
当TEX10与前核糖体结合时观察到的构造变化.

结论:

这些结构为人体基因组组合和功能提供了分子基础.
亚单元之间的特定相互作用对体的结构完整性和催化活性至关重要.
TEX10的形态可塑性表明它在核糖体生物发生过程中发挥了动态作用.

更多相关视频

Peering at Brain Polysomes with Atomic Force Microscopy

Peering at Brain Polysomes with Atomic Force Microscopy

Published on: March 16, 2016

Rapid Isolation of the Mitoribosome from HEK Cells

Rapid Isolation of the Mitoribosome from HEK Cells

Published on: October 4, 2018

相关概念视频

Ribosome Profiling

Ribosome Profiling

Ribosome profiling or ribo-sequencing is a deep sequencing technique that produces a snapshot of active translation in a cell. It selectively sequences the mRNAs protected by ribosomes to get an insight into a cell’s translation landscape at any given point in time.
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique...

Ribosomes

Ribosomes

Ribosomes translate genetic information encoded by messenger RNA (mRNA) into proteins. Both prokaryotic and eukaryotic cells have ribosomes. Cells that synthesize large quantities of protein—such as secretory cells in the human pancreas—can contain millions of ribosomes.
Ribosome Structure and Assembly
Ribosomes are composed of ribosomal RNA (rRNA) and proteins. In eukaryotes, rRNA is transcribed from genes in the nucleolus—a part of the nucleus that specializes in ribosome...

Termination of Translation

Termination of Translation

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...

Ribosomal RNA Synthesis

Ribosomal RNA Synthesis

Ribosome synthesis is a highly complex and coordinated process involving more than 200 assembly factors. The synthesis and processing of ribosomal components occurs not only in the nucleolus but also in the nucleoplasm and the cytoplasm of eukaryotic cells.
Ribosome biogenesis begins with the synthesis of 5S and 45S pre-rRNAs by distinct RNA polymerases. The primary transcripts are extensively processed and modified before they are bound and folded by ribosomal proteins and assembly factors,...

Nucleic Acids

Nucleic Acids

Nucleic acids are the most important macromolecules for the continuity of life. They carry the cell's genetic blueprint and carry instructions for its functioning.
DNA and RNA
The two main types of nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). DNA is the genetic material in all living organisms, ranging from single-celled bacteria to multicellular mammals. It is in the nucleus of eukaryotes and in the organelles, chloroplasts, and mitochondria. In prokaryotes,...

Improving Translational Accuracy

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...