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 basis of anaphylatoxin binding, activation, and signaling bias at complement receptors.
ジャーナル・号・ページ	Cell, Vol. 186, Issue 22, Page 4956-4973.e21, Year 2023
掲載日	2023年10月26日
著者	Manish K Yadav / Jagannath Maharana / Ravi Yadav / Shirsha Saha / Parishmita Sarma / Chahat Soni / Vinay Singh / Sayantan Saha / Manisankar Ganguly / Xaria X Li / Samanwita Mohapatra / Sudha Mishra / Htet A Khant / Mohamed Chami / Trent M Woodruff / Ramanuj Banerjee / Arun K Shukla / Cornelius Gati /
PubMed 要旨	The complement system is a critical part of our innate immune response, and the terminal products of this cascade, anaphylatoxins C3a and C5a, exert their physiological and pathophysiological ...The complement system is a critical part of our innate immune response, and the terminal products of this cascade, anaphylatoxins C3a and C5a, exert their physiological and pathophysiological responses primarily via two GPCRs, C3aR and C5aR1. However, the molecular mechanism of ligand recognition, activation, and signaling bias of these receptors remains mostly elusive. Here, we present nine cryo-EM structures of C3aR and C5aR1 activated by their natural and synthetic agonists, which reveal distinct binding pocket topologies of complement anaphylatoxins and provide key insights into receptor activation and transducer coupling. We also uncover the structural basis of a naturally occurring mechanism to dampen the inflammatory response of C5a via proteolytic cleavage of the terminal arginine and the G-protein signaling bias elicited by a peptide agonist of C3aR identified here. In summary, our study elucidates the innerworkings of the complement anaphylatoxin receptors and should facilitate structure-guided drug discovery to target these receptors in a spectrum of disorders.
リンク	Cell / PubMed:37852260 / PubMed Central
手法	EM (単粒子)
解像度	2.88 - 4.55 Å
構造データ	34943 8hpt EMDB-34943, PDB-8hpt: Structure of C5a-pep bound mouse C5aR1 in complex with Go 手法: EM (単粒子) / 解像度: 3.39 Å 34947 8hqc EMDB-34947, PDB-8hqc: Structure of a GPCR-G protein in complex with a natural peptide agonist 手法: EM (単粒子) / 解像度: 3.89 Å 35257 8i95 EMDB-35257, PDB-8i95: Structure of EP54-C3aR-Go complex 手法: EM (単粒子) / 解像度: 2.88 Å 35259 8i97 EMDB-35259, PDB-8i97: Structure of Apo-C3aR-Go complex (Glacios) 手法: EM (単粒子) / 解像度: 3.19 Å 35263 8i9a EMDB-35263, PDB-8i9a: Structure of EP54-C3aR-Gq complex 手法: EM (単粒子) / 解像度: 3.57 Å 35275 8i9l EMDB-35275, PDB-8i9l: Structure of C3a-C3aR-Go complex (Composite map) 手法: EM (単粒子) / 解像度: 3.18 Å 35282 8i9s EMDB-35282, PDB-8i9s: Structure of Apo-C3aR-Go complex (Titan) 手法: EM (単粒子) / 解像度: 3.26 Å 35292 8ia2 EMDB-35292, PDB-8ia2: Structure of C5a bound human C5aR1 in complex with Go (Composite map) 手法: EM (単粒子) / 解像度: 3.21 Å EMDB-35293: C3a-C3aR-Go (C3aR-Go complex only, Original Map) 手法: EM (単粒子) / 解像度: 3.18 Å EMDB-35294: C3a-C3aR-Go (C3a only, Original Map) 手法: EM (単粒子) / 解像度: 4.55 Å EMDB-35295: C5a-hC5aR1-Go (hC5aR1-Go complex only, Original map) 手法: EM (単粒子) / 解像度: 3.21 Å EMDB-35296: C5a-hC5aR1-Go complex (C5a only, Original map) 手法: EM (単粒子) / 解像度: 3.88 Å 36001 8j6d EMDB-36001, PDB-8j6d: Structure of EP141-C3aR-Go complex 手法: EM (単粒子) / 解像度: 3.1 Å 36755 8jzz EMDB-36755, PDB-8jzz: Structure of human C5a-desArg bound human C5aR1 in complex with Go 手法: EM (単粒子) / 解像度: 3.31 Å
由来	mus musculus (ハツカネズミ) homo sapiens (ヒト) synthetic construct (人工物)
キーワード	SIGNATLING PROTEIN/IMMUNE SYSTEM / GPCR / G protein / SIGNALING PROTEIN / SIGNATLING PROTEIN-IMMUNE SYSTEM complex / SIGNALING PROTEIN/IMMUNE SYSTEM / SIGNALING PROTEIN-IMMUNE SYSTEM complex / Cell Signaling / Immune system