对化疗受体的差异性CheR亲和力C-终端五调节化学反应反应
Félix Velando1, Elizabet Monteagudo-Cascales1, Miguel A Matilla1
1Department of Biotechnology and Environmental Protection, Estación Experimental del Zaidín, Consejo Superior de Investigaciones Científicas, Granada, Spain.
Molecular microbiology
|August 24, 2024
概括
细菌化学受体使用C端五来发送信号. 这些五序列的变化显著影响了CheR蛋白结合亲和力,并调节了化学反应反应,影响了相关和其他受体.
科学领域:
- 微生物学 微生物学
- 分子生物学分子生物学
- 生物化学 生化学
背景情况:
- 细菌中的化疗受体,如大肠杆菌,通常具有C端五基图案.
- 这种五型对于结合CheR和化CheB至关重要,在化学受体适应中发挥作用.
- 在细菌五中存在显著的序列变异,细菌经常具有具有不同五序列的多个化学受体.
研究的目的:
- 调查C端五序列的变化如何影响CheR结合亲和力.
- 为了确定五序列变异对细菌化学反应的影响.
- 为了利用Pectobacterium atrosepticum SCRI1043,一个拥有众多化学受体的细菌,作为一个模型系统.
主要方法:
- 对 Pectobacterium atrosepticum SCRI1043 中 36 种化学受体的分析,重点关注 19 种具有 C 末端五.
- 测量CheR与各种五序列的结合亲和力,量化解离常数 (KD).
- 基因操纵涉及切除cheR基因和替换PacC化学受体中的五.
主要成果:
- 对不同五的CheR亲和力变化多达11倍,高和低亲和力因单个氨基酸而异.
- 删除cheR基因完全取消了化疗.
- 用高或低亲和度变体修改PacC五,显著降低了对L-Asp的化学反应,也影响了L-Ser反应,但没有酸盐反应.
结论:
- C端五序列的变化直接影响了CheR结合亲和力.
- 五变化调节了同源受体的化学反应反应.
- 一个化学受体的五变化可以间接影响其他化学受体介导的化学反应.
相关概念视频
Chemotaxis and Direction of Cell Migration
3.3K
Cells can detect chemical cues in their environment and reorganize the cytoskeleton to migrate toward them or away from them. This directional migration, called chemotaxis, is essential during embryogenesis and development, immune response, tissue repair and regeneration, and reproduction. These chemical cues can either attract or repel the cell's movement. For example, axon development is determined by a combination of chemoattractants and chemorepellents that direct the growing axon...
3.3K
Cooperative 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
Adrenergic Agonists: Chemistry and Structure-Activity Relationship
2.6K
Adrenergic agonists' structure-activity relationship (SAR) determines their selectivity and efficacy. These agonists comprise a phenylethylamine moiety with an aromatic ring and an ethylamine side chain.
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of...
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of...
2.6K
The Two-State Receptor Model
1.9K
The two-state receptor model explains a drug's interaction with receptors, such as G protein-coupled receptors and ligand-gated ion channels, to induce or inhibit a biological response. When no natural ligands are present, a receptor exists in an equilibrium of inactive (Ri) and active (Ra) conformations. The inactive form does not produce a response, while the active form generates a basal effect known as constitutive activity.
The binding affinity of a drug determines its interaction with...
The binding affinity of a drug determines its interaction with...
1.9K
Direct-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship
908
Cholinergic agonists or cholinomimetics mimic the action of acetylcholine to stimulate the parasympathetic nervous system. They are categorized into direct-acting and indirect-acting agents. The direct-acting cholinergic drugs induce the parasympathetic response by directly binding to the muscarinic or nicotine receptors. In comparison, the indirect-acting cholinergic drugs prevent acetylcholine hydrolysis, indirectly contributing to the extended parasympathetic response.
The direct-acting...
The direct-acting...
908
Transducer Mechanism: G Protein–Coupled Receptors
1.9K
G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
GPCRs are also called heptahelical,...
GPCRs are also called heptahelical,...
1.9K


