关于酸酸3-酶催化和信号传导的结构性见解
E H Walker1, O Perisic, C Ried
1MRC Laboratory of Molecular Biology, MRC Centre, Cambridge, UK.
Nature
|December 2, 1999
概括
氨基酸3-激酶 (PI3Ks) 是参与细胞信号传递和贩运的脂质激酶. 该研究揭示了PI3Kgamma的X射线晶体结构,详细介绍了其模块化组织和潜在的全激活机制.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 氨基酸3-激酶 (PI3Ks) 是关键的脂类激酶,调节细胞信号传递,增殖,生存和贩运.
- PI3Ks具有双重的脂质和蛋白激酶活动,产生像PtdIns这样的第二信使{3,4,5) P3.3.
- 第I类PI3Kgamma被G蛋白贝塔亚单元和Ras激活,在细胞过程中发挥关键作用.
研究的目的:
- 为了阐明PI3K马函数的结构基础.
- 为了确定PI3Kgamma的催化子单元的X射线晶体结构.
- 了解酶的模块化组织和潜在的调节机制.
主要方法:
- 在X射线晶体学.
- 蛋白质结构的确定蛋白质结构的确定
- 生物化学分析 (隐含)
主要成果:
- 确定了PI3Kgamma的催化子单位的2.2 Å X射线晶体结构.
- PI3Kgamma表现出一个模块化组织,具有螺旋形域的脊柱.
- C2和催化域位于膜相互作用的位置,Ras结合域位于全激活的位置.
结论:
- 确定的结构为PI3Kgamma的膜相互作用和催化活性提供了洞察力.
- 拉斯结合域的位置表明,Ras. 通过Ras. 激活所有菌的机制.
- 这些结构信息对于理解PI3K信号通路和开发有针对性的治疗方法至关重要.
相关概念视频
Assembly of Signaling Complexes
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Amplifying Signals via Second Messengers
Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...
Amplifying Signals via Enzymatic Cascade
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 the...
IP3/DAG Signaling Pathway
Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and produces two-second...
Calmodulin-dependent Signaling
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,...
Signal Transduction: Overview
Cells respond to many types of information, often through receptor proteins positioned on the membrane. They respond to chemical signals, such as hormones, neurotransmitters, and other signaling molecules, initiating a series of molecular reactions to produce an appropriate response. This is called signal transduction. Cells also coordinate different responses elicited by the same signaling molecule via mediators, allowing molecular cross-talk.
Typically, signal transduction involves three...
Typically, signal transduction involves three...


