病毒杀手毒素的一个分子标:TOK1通道
1Department of Pediatrics, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Connecticut 06536, USA.
Cell
|November 11, 1999
概括
酵母中的K1杀手毒素激活TOK1通道,导致细胞死亡. 删除TOK1使酵母对这种毒素产生抵抗力.
科学领域:
- 分子生物学分子生物学
- 酵母遗传学 酵母遗传学
- 离子通道功能 离子通道功能
背景情况:
- 杀手菌株Saccharomyces cerevisiae具有病毒,并分泌蛋白质毒素.
- 这种K1杀手毒素向敏感的酵母细胞,破坏平衡,导致细胞死亡.
研究的目的:
- 阐明K1杀手毒素诱导细胞死亡的分子机制.
- 为了确定Saccharomyces cerevisiae中的K1杀手毒素的特定目标.
主要方法:
- 对Saccharomyces cerevisiae的基因操纵,包括基因删除和TOK1基因的过度表达.
- 对酵母细胞和Xenopus laevis卵细胞进行电生理学研究,以评估流和道活性.
- 从cDNA结构中表达K1毒素以研究其直接影响.
主要成果:
- 这种K1杀手毒素特别激活了Saccharomyces cerevisiae的血膜中的TOK1通道.
- 删除TOK1基因会对K1杀手毒素产生抗性.
- 过度表达TOK1会增加对毒素的敏感性.
- 在表达TOK1的细胞中观察到毒素诱导的流量,但在缺乏该基因的细胞中没有.
- K1毒素直接增加了TOK1通道的开放概率,独立于其他细胞因素.
结论:
- TOK1通道是K1杀手毒素的直接分子目标.
- 由K1毒素激活TOK1是Saccharomyces cerevisiae中K1毒素诱导的细胞死亡的主要原因.
相关概念视频
01:26Receptor Tyrosine Kinases
Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
01:20The 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...
01:36Types of Toxins
Humans continually engage with an environment rich in potentially harmful chemicals. These are introduced to our bodies through inhalation, ingestion, or skin contact. These chemicals exist in various forms, such as air and environmental pollutants, agricultural chemicals, organic solvents, and heavy metals.
Air pollutants, primarily gases, pose significant threats to respiratory health, leading to conditions like hypoxia, lung cancer, and in extreme cases, death.
Environmental pollutants like...
Air pollutants, primarily gases, pose significant threats to respiratory health, leading to conditions like hypoxia, lung cancer, and in extreme cases, death.
Environmental pollutants like...
01:27Transducer Mechanism: Enzyme-Linked Receptors
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include:
01:27Cytotoxic T Cells-mediated Immune Response
Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
01:12Bacterial Toxins
Bacterial toxins are sophisticated virulence factors that enable pathogenic bacteria to interact with, invade, and damage host tissues. These toxins fall broadly into two types: protein exotoxins, which are secreted into the environment and target specific host receptors, and lipopolysaccharide endotoxins, which are structural components of the bacterial outer membrane released primarily during bacterial lysis or membrane shedding. Exotoxins generally act more selectively, binding to cell...