GPCRの抗体エピトープの原子レベルマッピング
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
まとめ
ショットガン変異は,GPCR CCR5.5の抗体結合部位を正確にマッピングしました. このアプローチは,免疫支配的構造とその物理化学的性質を定義する重要なアミノ酸と原子を特定しました.
科学分野:
- 免疫学 免疫学とは
- 構造生物学 構造生物学とは
- バイオケミストリー バイオケミストリー
背景:
- Gタンパク質結合受容体 (GPCRs) などの統合膜タンパク質は,細胞信号伝達において重要な役割を果たします.
- これらの複雑なタンパク質のエピトープの描写は困難ですが,抗体相互作用を理解するために不可欠です.
- GPCR CCR5は,様々な疾患における重要な標的であり,その表位体のマッピングが重要である.
研究 の 目的:
- 統合膜タンパク質の抗体エピトープをマッピングするための高通量メソッドを開発し,適用する.
- CCR5.5を標的にするモノクローナル抗体の結合部位を構成する特定のアミノ酸および原子を特定する.
- CCR5.5の免疫支配領域の物理化学的特性を特徴づける.
主な方法:
- 系統的に変異を導入するために,高通量技術であるショットガン変異を生成した.
- 変異したCCR5変異体に対する5つの異なるモノクローン抗体の結合親和性を分析した.
- 抗体結合による相関変異データにより,重要なエピトープ残留物および原子を特定します.
主要な成果:
- CCR5.5に対する5つの異なるモノクローナル抗体の結合エピトープのマッピングに成功しました.
- 特定された特定のアミノ酸残留物,およびいくつかの場合,抗体の認識に不可欠な個々の原子.
- CCR5.5における免疫支配的エピトープの物理化学的性質についての洞察を提供した.
結論:
- ショットガン突然変異は,複雑な統合膜タンパク質のエピトープマッピングのための効果的な高通量アプローチです.
- この研究では,特定の抗体によって認識されるCCR5の免疫支配的構造を正確に定義しました.
- この詳細なエピトープ情報は,ターゲットを絞った治療法と診断法の開発に役立ちます.
関連する概念動画
01:10Antibody 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...
01:10Antibody 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...
01:15G 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...
01:25Antibody 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.
01:30Transducer 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...