3VG9

Crystal structure of human adenosine A2A receptor with an allosteric inverse-agonist antibody at 2.7 A resolution

3VG9 の概要

• エントリーDOI: 10.2210/pdb3vg9/pdb
• 関連するPDBエントリー: 3VGA
• 分子名称: Adenosine receptor A2a, antibody fab fragment light chain, antibody fab fragment heavy chain, ... (7 entities in total)
• 機能のキーワード: 7 transmembrane receptor, signal transduction, signaling protein
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cell membrane; Multi-pass membrane protein: P29274
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 86917.91

構造登録者

Hino, T.,Arakawa, T.,Iwanari, H.,Yurugi-Kobayashi, T.,Ikeda-Suno, C.,Nakada-Nakura, Y.,Kusano-Arai, O.,Weyand, S.,Shimamura, T.,Nomura, N.,Cameron, A.D.,Kobayashi, T.,Hamakubo, T.,Iwata, S.,Murata, T. (登録日: 2011-08-04, 公開日: 2012-02-01, 最終更新日: 2023-11-08)

主引用文献

Hino, T.,Arakawa, T.,Iwanari, H.,Yurugi-Kobayashi, T.,Ikeda-Suno, C.,Nakada-Nakura, Y.,Kusano-Arai, O.,Weyand, S.,Shimamura, T.,Nomura, N.,Cameron, A.D.,Kobayashi, T.,Hamakubo, T.,Iwata, S.,Murata, T.
G-protein-coupled receptor inactivation by an allosteric inverse-agonist antibody
Nature, 482:237-240, 2012

PubMed Abstract: G-protein-coupled receptors are the largest class of cell-surface receptors, and these membrane proteins exist in equilibrium between inactive and active states. Conformational changes induced by extracellular ligands binding to G-protein-coupled receptors result in a cellular response through the activation of G proteins. The A(2A) adenosine receptor (A(2A)AR) is responsible for regulating blood flow to the cardiac muscle and is important in the regulation of glutamate and dopamine release in the brain. Here we report the raising of a mouse monoclonal antibody against human A(2A)AR that prevents agonist but not antagonist binding to the extracellular ligand-binding pocket, and describe the structure of A(2A)AR in complex with the antibody Fab fragment (Fab2838). This structure reveals that Fab2838 recognizes the intracellular surface of A(2A)AR and that its complementarity-determining region, CDR-H3, penetrates into the receptor. CDR-H3 is located in a similar position to the G-protein carboxy-terminal fragment in the active opsin structure and to CDR-3 of the nanobody in the active β(2)-adrenergic receptor structure, but locks A(2A)AR in an inactive conformation. These results suggest a new strategy to modulate the activity of G-protein-coupled receptors.

PubMed: 22286059
DOI: 10.1038/nature10750

実験手法

X-RAY DIFFRACTION (2.7 Å)