一个PDZ-酶性继电器介导PAR复合体调节器交换
Elizabeth Vargas1, Rhiannon R Penkert1, Kenneth E Prehoda1
1Institute of Molecular Biology, Department of Chemistry and Biochemistry, 1229 University of Oregon, Eugene, OR 97403.
bioRxiv : the preprint server for biology
|October 28, 2024
概括
对于细胞极化至关重要的Par复合体,涉及非典型的蛋白激酶C (aPKC),Cdc42和Par-3. 这项研究揭示了一种连接Cdc42和Par-3结合的异质中继机制,解释了Par复合物的活性.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 帕尔复合物通过非典型的蛋白激酶C (aPKC) 调节动物细胞中的细胞极性.
- Cdc42和Par-3是上游调节器,它们单独与Par复合体结合,影响其活动.
- 由于Cdc42和Par-3具有不同的绑定位置,因此引发了关于它们的交叉监管的问题.
研究的目的:
- 调查Cdc42,Par-3和Par复合体之间的监管相互作用.
- 阐明了对aPKC的Par-3结合被调节的机制.
- 了解这些相互作用如何促进PAR复杂介导细胞极化.
主要方法:
- 生物化学测试用于研究蛋白质相互作用.
- 在aPKC内对自身抑制机制的分析.
- 调查Par-6 PDZ域在调节aPKC活动中的作用.
主要成果:
- 对aPKC的Par-3结合由aPKC的自身抑制来调节.
- Par-6 PDZ域通过与aPKC激酶域的新型相互作用激活aPKC与Par-3结合.
- Cdc42 和 Par-3 对 Par-6 PDZ-aPKC 激酶相互作用产生相反的作用,建立一个全继电器.
结论:
- 一个全osteric继电器机制连接Cdc42和Par-3结合点在Par复合体内.
- 这种继电器涉及对Par-6 PDZ-aPKC激酶相互作用的差异性影响,是Par复合物的极化和活性所必需的负合作性的基础.
相关概念视频
01:58Cooperative Allosteric Transitions
7.9K
Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
7.9K
01:22Amplifying 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
01:30Assembly of Signaling Complexes
5.7K
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,...
5.7K
01:11IP3/DAG Signaling Pathway
11.9K
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...
11.9K
01:19Interactions Between Signaling Pathways
6.2K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.2K
01:16Calmodulin-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