直接观察底层的动态过程 体信号传输的直接观察
Sven Brüschweiler1, Paul Schanda, Karin Kloiber
1Department of Computational & Structural Biology, Max F. Perutz Laboratories, Campus Vienna Biocenter 5, A-1030 Vienna, Austria.
Journal of the American Chemical Society
|February 11, 2009
概括
类蛋白质使用动态形状变化来传输信号. 研究人员观察了CREB结合蛋白的KIX域如何传递全信息,揭示了信号传输的保存途径.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 分子生物物理学 分子生物物理学
背景情况:
- 体调节对于生物控制至关重要,涉及通过蛋白质结构传输信号.
- CREB结合蛋白的KIX域通过两个不同的结合位点调解转录因子之间的合作.
研究的目的:
- 直接观察KIX域内的全osteric信息通信的动态过程.
- 阐明KIX调解转录因子之间合作的机制.
主要方法:
- 利用NMR放松分散技术研究蛋白质动力学.
- 研究了KIX域在与混合血统白血病 (MLL) 转录因子结合时的结构变化.
主要成果:
- 观察到在MLL结合时,KIX形状的再分配向高能状态,预先形成全结合位.
- 标志着全沟通过程,发生在27°C的3毫秒时间常数下.
- 确定了一个进化保守的疏水性氨基酸网络作为信息传输途径.
结论:
- MLL与KIX的结合诱导了与莫诺德 - 怀曼 - 切克斯 (WMC) 全雌激素模型相一致的构造变化.
- 所有的信息都通过一个动态的结构重组来传递,其中包括一个保存的疏水网络.
- 核磁共振放松分散提供了对全调节的动态机制的直接洞察.
相关概念视频
Allosteric Regulation
Allosteric regulation of enzymes occurs when the binding of an effector molecule to a site that is different from the active site causes a change in the enzymatic activity. This alternate site is called an allosteric site, and an enzyme can contain more than one of these sites. Allosteric regulation can either be positive or negative, resulting in an increase or decrease in enzyme activity. Most enzymes that display allosteric regulation are metabolic enzymes involved in the degradation or...
Allosteric Regulation
Allosteric regulation of enzymes occurs when the binding of an effector molecule to a site that is different from the active site causes a change in the enzymatic activity. This alternate site is called an allosteric site, and an enzyme can contain more than one of these sites. Allosteric regulation can either be positive or negative, resulting in an increase or decrease in enzyme activity. Most enzymes that display allosteric regulation are metabolic enzymes involved in the degradation or...
Cooperative Allosteric Transitions
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...
Cooperative Allosteric Transitions
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...
Cooperative Allosteric Transitions
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...
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...


