hGBP3的螺旋域不能刺激GTP的第二次酸盐裂解
Divya Rashmi1, Sowmiya Gupta1, Tasneem Kausar1
1Protein Engineering Laboratory, National Institute of Immunology, New Delhi, India.
The Journal of biological chemistry
|February 1, 2024
概括
人体酸结合蛋白 (hGBPs) 是免疫的关键. 与hGBP1不同,hGBP3由于其催化域缺乏构造变化,导致GMP产生减少,从而阻碍了其抗病原和抗瘤功能.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 干扰因子-诱导的大型GTPase (hGBPs) 对细胞免疫至关重要,表现出抗病原和抗瘤活性.
- hGBP3是hGBP1的同源,具有N端催化和C端螺旋域,但其特定的生物化学功能和在GTP水解中的域作用尚不清楚.
研究的目的:
- 调查hGBP3的生物化学功能,并阐明其域在瓜诺辛三酸盐 (GTP) 水解中的作用.
- 与hGBP1.1相比,了解hGBP3独特的GMP生产的分子基础.
主要方法:
- 用hGBP3及其截断变体测量GDP和GMP生产的生物化学分析.
- 计算和解决方案研究来分析蛋白质结构和动态.
- 位点定向突变发生,以检查像W79.9这样的特定残留物的作用.
主要成果:
- 与hGBP1 (85%) 相比,hGBP3产生明显较少的GMP (30%),这表明二次酸盐分裂受损.
- 状域的删除没有改变GMP生产,这表明它不会刺激hGBP3.3中的第二个GTP裂变.
- 在hGBP3的催化域中的调节残留物W79未能在GTP水解后诱导有效形成GMP所需的构造变化.
结论:
- hGBP3的螺旋域不能有效地调解催化循环运动所需的域间接触,导致GMP形成减少.
- 催化域的这种形态不灵活性导致hGBP3的GMP产量较低,影响其免疫功能.
相关概念视频
GTPases and their Regulation
8.4K
Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒ small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins,...
Large G-proteins,...
8.4K
Activation and Inactivation of G Proteins
7.2K
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...
7.2K
Mechanical Protein Functions
4.9K
Proteins perform many mechanical functions in a cell. These proteins can be classified into two general categories- proteins that generate mechanical forces and proteins that are subjected to mechanical forces. Proteins providing mechanical support to the structure of the cell, such as keratin, are subjected to mechanical force, whereas proteins involved in cell movement and transport of molecules across cell membranes, such as an ion pump, are examples of generating mechanical force.
4.9K
ATP Synthase: Mechanism
14.6K
In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased...
14.6K
Amplifying Signals via Enzymatic Cascade
8.5K
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
8.5K
Small GTPases - Ras and Rho
4.0K
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:
Three regulatory proteins control their activity:
4.0K


