铁素64酸化对Ras的深远影响与BeF3-复合体一起被揭示出来
Patrick Baumann1,2,3, Yi Jin4,5,6
1School of Chemistry, Cardiff University, Park Place, Cardiff, CF10 3AT, UK.
Communications chemistry
|January 31, 2024
概括
由Src酶对Ras蛋白的氨酸酸化改变了它的构造,影响了它的相互作用. 这项研究揭示了铁素64的酸化如何影响Ras蛋白的结构和功能.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 已知Ras蛋白的 Src 激酶介导的氨酸酸化会破坏其调节和通信通路.
- 这种酸化影响Ras相互作用的确切机制尚不清楚.
研究的目的:
- 通过氨酸酸化阐明Ras调节的结构和机制基础.
- 为了研究 Ras 蛋白质在 tyrosine64 的酸化引起的构造变化.
主要方法:
- 使用31P核磁共振 (NMR) 和突变发生的tyrosine64单酸化的量化.
- 确定非化和化Ras-BeF3-复合物的晶体结构.
- 使用19F NMR进行形状变化的分析.
主要成果:
- 晶体结构揭示了化Ras的明显"封闭"形状,与之前观察到的"开放"形状不同.
- 在氨酸64的酸化引起了远程的形状变化,减少了对下游效应物的亲和力Raf.
- 19F NMR显示了改变的内在GTPase和核酸交换率,主要的"关闭"和较小的"开放"构造都存在.
结论:
- 铁素64的酸化会诱导Ras蛋白的显著构造变化,影响其功能相互作用.
- 金属化物复合物是研究改性Ras蛋白的结构动态的有效工具.
- 这项研究为Ras内在GTP水解和调节提供了新的机制性见解.
相关概念视频
The Ras Gene
6.2K
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...
Ras is a...
6.2K
MAPK Signaling Cascades
5.5K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.5K
Receptor Tyrosine Kinases
12.9K
Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
12.9K
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
PI3K/mTOR/AKT Signaling Pathway
3.6K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.6K
Enzyme-linked Receptors
78.4K
Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
78.4K


