晶体结构的整体膜的二甲酸甘油激酶
Dianfan Li1, Joseph A Lyons, Valerie E Pye
1School of Biochemistry and Immunology & School of Medicine, Trinity College Dublin, Dublin 2, Ireland.
Nature
|May 17, 2013
概括
一个模型的膜酶 - - 甲基糖酶 (diacylglycerol kinase) 在结构上进行了表征. 晶体结构揭示了其 homo-trimeric 形式和活性位点,与之前的模型不同.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 膜蛋白酶学 膜蛋白酶学
背景情况:
- 糖醇激酶 (DGK) 对于阴性细菌的细胞包膜合成至关重要,催化糖醇酸化到酸.
- 这种121残留酶是研究膜蛋白酶学,折叠,组装和稳定性的长期模型.
研究的目的:
- 为呈现三种功能形式的二甲基甘油激酶的高分辨率晶体结构.
- 为了阐明酶的同型三聚体结构,活性部位和基质/辅因子结合.
主要方法:
- 采用X射线晶体学来确定野生类型和突变型二甲基甘油激酶的结构.
- 结构分析的重点是确定活性部位,跨膜域和寡合体状态.
主要成果:
- 三个晶体结构揭示了一个同三位数的二甲基甘油酶,每个单体具有三个跨膜螺旋和一个N端的两螺旋.
- 这些结构识别出一个复合的,与结合的脂质基质和对接的ATP共享的活性位点.
- 这些晶体结构与关于域互换的已发表的解决方案NMR模型不一致.
结论:
- 晶体结构为了解二甲基甘激酶的功能和机制提供了详细的分子基础.
- 这些发现合理化了关于这个模型酶的大量现有生物化学和生物物理数据.
- 观察到的结构与以前的解决方案状态模型相矛盾,强调了结构上下文的重要性.
相关概念视频
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...
Activation and Inactivation of G Proteins
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 affinity and are together...
Pinching-off of Coated Vesicles
Vesicle budding is orchestrated by distinct cytosolic proteins such as adaptor proteins, coat proteins, and GTPases. To initiate vesicle budding, membrane-bending proteins containing crescent-shaped BAR domains bind to the lipid heads in the bilayer and distort the membrane to form a protein-coated vesicle bud. Adaptors proteins such as AP2 for clathrin-coated vesicles can nucleate on the deformed membrane. Finally, coat proteins such as clathrin or COPI and COPII assemble into a coat forming...
Lipids as Anchors
In the plasma membrane, the lipids forming the bilayer can also act as an anchor to tether proteins to the membrane. The three main types of lipid anchors found in eukaryotes are – prenyl groups, fatty acyl groups, and glycosylphosphatidylinositol or GPI groups. Prenyl and fatty acyl groups act as anchors on the cytosolic surface of the membrane, whereas GPI anchors proteins on the extracellular side.
The carboxy-terminal of most of the prenylated proteins, such as Ras proteins, contains the...
The carboxy-terminal of most of the prenylated proteins, such as Ras proteins, contains the...
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,...
ATP Synthase: Structure
ATP synthase or ATPase is among the most conserved proteins found in bacteria, mammals, and plants. This enzyme can catalyze a forward reaction in response to the electrochemical gradient, producing ATP from ADP and inorganic phosphate. ATP synthase can also work in a reverse direction by hydrolyzing ATP and generating an electrochemical gradient. Different forms of ATP synthases have evolved special features to meet the specific demands of the cell. Based on their specific feature, ATP...


