在GPCR上对抗体表位的原子水平映射
Cheryl Paes1, Jada Ingalls, Karan Kampani
1Integral Molecular, Inc., 3701 Market Street, Fourth Floor, Philadelphia, Pennsylvania 19104, USA.
Journal of the American Chemical Society
|May 21, 2009
概括
枪枪突变发生精确地绘制了GPCR CCR5.5上的抗体结合部位. 这种方法确定了关键的氨基酸和原子,定义了免疫主导结构及其物理化学性质.
科学领域:
- 免疫学 免疫学 免疫学
- 结构生物学 结构生物学
- 生物化学 生物化学
背景情况:
- 整体膜蛋白,如G蛋白合受体 (GPCRs),在细胞信号传递中起着至关重要的作用.
- 在这些复杂的蛋白质上划分表位是具有挑战性的,但对于理解抗体相互作用至关重要.
- 在各种疾病中,GPCR CCR5 是一个重要的标,使其表位图的绘制变得非常重要.
研究的目的:
- 开发和应用一种高通量方法,用于在整体膜蛋白上映射抗体表位.
- 识别构成针对CCR5.5的单克隆抗体结合点的特定氨基酸和原子.
- 描述CCR5.5免疫主导区域的物理化学特性.
主要方法:
- 利用枪支突变发生,一种高吞吐量技术,系统地引入突变.
- 分析了五种不同的单克隆抗体与突变的CCR5变体的结合亲和力.
- 与抗体结合相关的突变数据,以确定关键的表位残留物和原子.
主要成果:
- 成功地绘制了针对CCR5.5的五种不同的单克隆抗体的结合表位.
- 确定了特定的氨基酸残留物,在某些情况下,单个原子,对于抗体识别至关重要.
- 提供了关于CCR5.5上免疫主导表位的物理化学性质的见解.
结论:
- 枪枪突变发生是一种有效的高通量方法,用于复杂的整体膜蛋白的表位图绘制.
- 该研究精确地定义了由特定抗体识别的CCR5的免疫主导结构.
- 这些详细的表位信息可以为开发向治疗和诊断提供信息.
相关概念视频
Antibody Structure
Overview
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
Antibody Structure
Overview
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
G Protein-coupled Receptors
G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
Antibody Structure and Classes
Antibodies, also known as immunoglobulins, are produced by B cells in response to foreign substances, such as bacteria and viruses. These proteins are critical for recognizing and neutralizing these substances, protecting the body from potential harm.
The basic structure of an antibody consists of four protein chains: two identical heavy chains and two identical light chains. These chains are held together by disulfide bonds and other non-covalent interactions, forming a Y-shaped structure.
The basic structure of an antibody consists of four protein chains: two identical heavy chains and two identical light chains. These chains are held together by disulfide bonds and other non-covalent interactions, forming a Y-shaped structure.
Transducer Mechanism: G Protein–Coupled Receptors
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, 7TM, or...
GPCRs are also called heptahelical, 7TM, or...

