相关实验视频

Updated: Jun 4, 2025

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease

Published on: April 4, 2018

在RhoA基因中的致病性单核酸多态:透视通过分子动力学模拟对RhoA-PLD1相互作用的结构和功能影响

Mahbub Hasan¹, Md Nayem Sarker¹, Tazkia Jabin¹

¹Department of Biochemistry and Molecular Biology, Shahjalal University of Science and Technology, Sylhet, 3114, Bangladesh.

Current research in structural biology

|December 19, 2024

概括

在RhoA基因中使用计算工具识别的有害单核酸多态 (SNP) 可能会破坏GTP结合和蛋白相互作用,可能会影响疾病的发展并提供治疗点.

科学领域:

分子生物学和遗传学分子生物学和遗传学
计算生物学和生物信息学
结构生物学是结构生物学.

背景情况:

像RhoA (Ras同源基因家族成员A) 这样的分子开关对于信号传导至关重要.
异常的RhoA功能,通常是由于遗传变异,与各种疾病有关.
单核酸多态 (SNP) 在RhoA中可以改变蛋白质结构和功能,影响病原性.

研究的目的:

在RhoA基因中计算选有害的非同义SNP (nsSNP).
调查已识别的有害RhoA突变的结构和功能影响.
探索这些突变在RhoA-GDP-PLD1复杂相互作用和疾病中的潜在作用.

主要方法:

使用七种不同的计算工具对207个RhoA nsSNP进行选.
在保护区域中发现的常见有害SNP的识别和GTP结合动机.
结构分析选择的RhoA突变和RhoA-GDP-PLD1复合体的250 ns分子动力学 (MD) 模拟.

主要成果:

确定了8种常见的有害SNP,其中5种 (V9G,G17E,E40K,A61T,F171L) 存在于保护区.
突变E40K和A61T可能会影响GTP/GDP结合,因为它们位于关键基因中.
MD模拟显示了RhoA-GDP-PLD1复合体中的G17E和I86N突变的结构不稳定性和改变的相互作用.

结论:

有害的RhoA SNPs,特别是G17E和I86N,可以显著影响蛋白质结构和相互作用.
这些突变可能会影响RhoA与PLD1的相互作用,PLD1是血栓形成和癌症的关键调节者.
需要进一步的体外和体内研究来验证这些发现作为潜在的生物标志物和治疗点.

关键词:

有害的SNP可能会造成损害.分子动态模拟分子动态模拟分子切换是指分子的切换.在RhoAAA 罗亚-GDP-PLD1 的时间

更多相关视频

Author Spotlight: Advancing the Detection of Low-Frequency Mutations in Cancer Tissues

Author Spotlight: Advancing the Detection of Low-Frequency Mutations in Cancer Tissues

Published on: August 23, 2024

Optogenetic Phase Transition of TDP-43 in Spinal Motor Neurons of Zebrafish Larvae

Optogenetic Phase Transition of TDP-43 in Spinal Motor Neurons of Zebrafish Larvae

Published on: February 25, 2022

相关概念视频

Small GTPases - Ras and Rho

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:

The Ras Gene

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...

Single Nucleotide Polymorphisms-SNPs

Single Nucleotide Polymorphisms-SNPs

A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...

Cell Polarization by Rho Proteins

Cell Polarization by Rho Proteins

Cell polarity is the asymmetric distribution of cellular and membrane components, making one side of the cell different from the other. This polarity is essential to many processes such as embryogenesis, axon migration, glucose transport across epithelial cells, and directional cell migration. A migrating cell responds to intracellular or extracellular signals via molecular cascades that reorganize the actin cytoskeleton to establish this polarity. In these cells, the Rho family proteins Cdc42,...