识别关键酸化部位,以双模融合框架增强激酶活性
Menghuan Zhang1, Yizhi Zhang1, Keqin Dong2
1State Key Laboratory of Cardiovascular Diseases and Medical Innovation Center, Institute for Regenerative Medicine, Department of Neurosurgery, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Molecular & cellular proteomics : MCP
|December 1, 2024
概括
研究人员开发了一种新的计算方法,以找到激酶上的关键酸化位,以提高其活性. 这种方法成功地发现了77个新位点,推动了酶研究.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 生物信息学是一种生物信息学.
背景情况:
- 酸化是一种关键的细胞过程,调节蛋白质功能,特别是酶活性.
- 关键酸化位点 (phos位点) 增强激酶活性,但许多仍未被发现.
- 现有的方法缺乏系统的计算方法来识别这些关键的位.
研究的目的:
- 开发了第一个系统的计算方法来识别酶上的关键位.
- 为了利用酸化质谱和蛋白质序列数据进行增强的预测.
- 发现可显著增强激酶活性的新型位.
主要方法:
- 介绍了PhoSiteformer,这是一个以变压器为灵感的模型,用于从质谱数据中生成位嵌入.
- 开发了CSPred,一种使用双模融合策略的分类模型.
- 结合PhoSiteformer嵌入式与蛋白质语言模型 (ProtT5) 嵌入式.
主要成果:
- 在58个人体酶上成功识别了77个关键位.
- 通过实验验证了两个新网站:PKG1上的T517和PRKD3.3上的T735.
- 证明了双模聚变策略在预测关键位的有效性.
结论:
- 提出了第一个系统的计算方法来识别激酶激活位.
- PhoSiteformer和CSPred为探索酶调节提供了一个强大的工具.
- 这些已识别的位点为了解和操纵酶功能提供了新的目标.
相关概念视频
Amplifying Signals via Enzymatic Cascade
8.3K
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...
8.3K
Protein Kinases and Phosphatases
13.1K
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
13.1K
PI3K/mTOR/AKT Signaling Pathway
3.4K
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...
3.4K
Phosphorylation
50.0K
The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
50.0K
MAPK Signaling Cascades
5.2K
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...
5.2K
Calmodulin-dependent Signaling
5.1K
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
5.1K


