压力传感器PDZ蛋白酶DegS的Allosteric激活,这是一个压力传感器PDZ蛋白酶
Jungsan Sohn1, Robert A Grant, Robert T Sauer
1Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Cell
|November 6, 2007
概括
外膜蛋白 (OMP) 结合通过一种全osteric 机制激活DegS蛋白酶,将其切换到功能状态. 这种类似开关的行为对于大肠杆菌的信号传导至关重要.
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:
- 调节的内膜蛋白解 (RIP) 是细胞间的关键信号传递机制.
- 在大肠杆菌中,受损的周等离子蛋白折叠触发了外膜蛋白 (OMPs) 激活DegS蛋白酶的过程.
- DegS通过跨膜调节器RseA进行裂变,从而启动一个信号级联.
研究的目的:
- 阐明OMPs对DegS蛋白酶激活的全性机制.
- 了解DegS交换机类行为的结构和功能基础.
- 为了研究这种全激活机制在相关蛋白酶中的保存.
主要方法:
- 进行X射线晶体学以确定DegS结构.
- 生化分析测量蛋白酶活性.
- 突变性研究以确定涉及全调节的关键残留物.
主要成果:
- 德格斯作为一种全酶起作用,在OMP结合时从无活性转变为活性构成.
- 德格斯的未结合的PDZ域是抑制性的;OMP结合稳定了活性构造.
- 无论是OMP诱导的激活还是RseA绑定都表现出积极的合作性,使交换式响应成为可能.
- 在DegP/HtrA和HtrA2/Omi蛋白酶家族中保存了关键的全菌残留物.
结论:
- 对OMP的结合足以以全osterically激活DegS蛋白酶.
- 由于积极的合作性,OMP-DegS-RseA系统显示了类似交换机的特性.
- 一种常见的全激活机制可能是许多PDZ蛋白酶的功能基础.
相关概念视频
The Unfolded Protein Response
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
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...
The JAK-STAT Signaling Pathway
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
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...
GPCRs Regulate Adenylyl Cylase Activity
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Two...
Other Stress Responses in Bacteria
Bacteria have global regulatory systems that control several types of stress mechanisms. These include Pho regulon and the heat shock response, which are essential systems for environmental adaptation, such as nutrient limitation and proteotoxic stress. The Pho regulon and the heat shock response exemplify bacterial resilience, enabling rapid adaptation to fluctuating environmental conditions.Pho RegulonBacteria require phosphorus for essential cellular processes, including nucleic acid...


