EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Molecular mechanisms of naturally encoded signaling bias at the complement anaphylatoxin receptors.
ジャーナル・号・ページ	Mol Cell, Vol. 86, Issue 13, Page 2586-2604.e14, Year 2026
掲載日	2026年7月2日
著者	Divyanshu Tiwari / Kazuhiro Sawada / Annu Dalal / Sudha Mishra / Xaria X Li / Joshua C Dent / Kiae Kim / Manish K Yadav / Nabarun Roy / Manisankar Ganguly / Nilanjana Banerjee / Tomasz Maciej Stepniewski / Donghoon Ahn / Kohei Yamaguchi / Hidetaka S Oshima / Kana Hashimoto / Jenny N Fung / Titaya Lerskiatiphanich / Cedric S Cui / John D Lee / Jana Selent / Asuka Inoue / Richard J Clark / Ka Young Chung / Ramanuj Banerjee / Fumiya K Sano / Trent M Woodruff / Osamu Nureki / Arun K Shukla /
PubMed 要旨	The conceptual framework of biased agonism has greatly impacted our understanding of G-protein-coupled receptor (GPCR) signaling, regulatory paradigms, and drug discovery efforts. Here, we present ...The conceptual framework of biased agonism has greatly impacted our understanding of G-protein-coupled receptor (GPCR) signaling, regulatory paradigms, and drug discovery efforts. Here, we present fundamental molecular and structural insights into intrinsic bias encoded at the human and mouse complement anaphylatoxin C5a receptors, namely C5aR1 and C5aR2. We discover that a naturally occurring version of C5a, i.e., C5a, exhibits a robust G-protein-coupling bias at C5aR1 with attenuated β-arrestin (βarr) recruitment, which originates from a distinct conformation of TM7 and helix 8 in the receptor, leading to inefficient GRK recruitment and phosphorylation. We also determine a series of cryo-electron microscopy (cryo-EM) structures of C5aR2, a naturally encoded βarr-biased receptor, which uncover key differences in anaphylatoxin recognition by C5aR2 relative to C5aR1. These structural snapshots also uncover a shallower cytoplasmic pocket in C5aR2 with a hydrophobic interior, which is likely incompatible with efficient G-protein coupling, leading to intrinsic bias. Our findings illuminate the molecular basis of naturally encoded signaling bias at GPCRs, with direct implications for therapeutic design.
リンク	Mol Cell / PubMed:42330960
手法	EM (単粒子)
解像度	2.97 - 3.82 Å
構造データ	64749 9v35 EMDB-64749, PDB-9v35: Structure of C5a anaphylatoxin chemotactic receptor 2, C5aR2 in the Apo state 手法: EM (単粒子) / 解像度: 2.97 Å 64751 9v38 EMDB-64751, PDB-9v38: Structure of C5a anaphylatoxin chemotactic receptor 2, C5aR2 bound to EP54 手法: EM (単粒子) / 解像度: 3.25 Å 64752 9v3c EMDB-64752, PDB-9v3c: Structure of C5a anaphylatoxin chemotactic receptor 2, C5aR2 bound to C5a 手法: EM (単粒子) / 解像度: 3.82 Å 64761 9v3y EMDB-64761, PDB-9v3y: Structure of C5a anaphylatoxin chemotactic receptor 2, C5aR2 bound to C5a-pep 手法: EM (単粒子) / 解像度: 3.06 Å 64777 9v4d EMDB-64777, PDB-9v4d: Structure of C5a anaphylatoxin chemotactic receptor 2, C5aR2 bound to R8Y 手法: EM (単粒子) / 解像度: 3.07 Å 65890 9wdi EMDB-65890, PDB-9wdi: Structure of mC5aR2 in complex with mC5a-desArg 手法: EM (単粒子) / 解像度: 3.33 Å 80132 25if EMDB-80132, PDB-25if: Structure of mC5aR2 in complex with mC5a-desArg (Monomer) 手法: EM (単粒子) / 解像度: 3.42 Å
由来	homo sapiens (ヒト) mus musculus (ハツカネズミ)
キーワード	SIGNALING PROTEIN / G protein coupled receptor / G protein / Membrane protein / Immunite system