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	Structure-based design of non-hypertrophic apelin receptor modulator.
ジャーナル・号・ページ	Cell, Vol. 187, Issue 6, Page 1460-1475.e20, Year 2024
掲載日	2024年3月14日
著者	Wei-Wei Wang / Su-Yu Ji / Wenjia Zhang / Junxia Zhang / Chenxi Cai / Rubi Hu / Shao-Kun Zang / Luwei Miao / Haomang Xu / Li-Nan Chen / Zongkuai Yang / Jia Guo / Jiao Qin / Dan-Dan Shen / Ping Liang / Yan Zhang / Yan Zhang /
PubMed 要旨	Apelin is a key hormone in cardiovascular homeostasis that activates the apelin receptor (APLNR), which is regarded as a promising therapeutic target for cardiovascular disease. However, adverse ...Apelin is a key hormone in cardiovascular homeostasis that activates the apelin receptor (APLNR), which is regarded as a promising therapeutic target for cardiovascular disease. However, adverse effects through the β-arrestin pathway limit its pharmacological use. Here, we report cryoelectron microscopy (cryo-EM) structures of APLNR-G complexes bound to three agonists with divergent signaling profiles. Combined with functional assays, we have identified "twin hotspots" in APLNR as key determinants for signaling bias, guiding the rational design of two exclusive G-protein-biased agonists WN353 and WN561. Cryo-EM structures of WN353- and WN561-stimulated APLNR-G protein complexes further confirm that the designed ligands adopt the desired poses. Pathophysiological experiments have provided evidence that WN561 demonstrates superior therapeutic effects against cardiac hypertrophy and reduced adverse effects compared with the established APLNR agonists. In summary, our designed APLNR modulator may facilitate the development of next-generation cardiovascular medications.
リンク	Cell / PubMed:38428423
手法	EM (単粒子)
解像度	2.4 - 3.2 Å
構造データ	38794 8xzf EMDB-38794, PDB-8xzf: Cryo-EM structure of the WN561-bound human APLNR-Gi complex 手法: EM (単粒子) / 解像度: 3.0 Å 38795 8xzg EMDB-38795, PDB-8xzg: Cryo-EM structure of the [Pyr1]-apelin-13-bound human APLNR-Gi complex 手法: EM (単粒子) / 解像度: 3.2 Å 38796 8xzh EMDB-38796, PDB-8xzh: Cryo-EM structure of the MM07-bound human APLNR-Gi complex 手法: EM (単粒子) / 解像度: 2.6 Å 38797 8xzi EMDB-38797, PDB-8xzi: Cryo-EM structure of the CMF-019-bound human APLNR-Gi complex 手法: EM (単粒子) / 解像度: 2.7 Å 38798 8xzj EMDB-38798, PDB-8xzj: Cryo-EM structure of the WN353-bound human APLNR-Gi complex 手法: EM (単粒子) / 解像度: 3.0 Å EMDB-38967: The focused refinement map (Receptor) of the MM07 bound APLNR-Gi1 structure. 手法: EM (単粒子) / 解像度: 2.6 Å EMDB-38969: The focused refinement map (G-protein) of MM07 bound APLNR-Gi1 structure. 手法: EM (単粒子) / 解像度: 2.4 Å EMDB-38970: The low resolution consensus map of the MM07 bound APLNR-Gi1 structure. 手法: EM (単粒子) / 解像度: 2.5 Å EMDB-38971: The focused refinement map (Receptor) of CMF-019 bound APLNR-Gi1 structure. 手法: EM (単粒子) / 解像度: 2.7 Å EMDB-38972: The focused refinement map (G-protein) of CMF-019 bound APLNR-Gi1 structure. 手法: EM (単粒子) / 解像度: 2.5 Å EMDB-38973: CMF-019 bound APLNR complex 手法: EM (単粒子) / 解像度: 2.7 Å EMDB-38974: The focused refinement map (Receptor) of WN353 bound APLNR-Gi1 structure 手法: EM (単粒子) / 解像度: 3.0 Å EMDB-38975: The focused refinement map (G-protein) of WN353 bound APLNR-Gi1 structure 手法: EM (単粒子) / 解像度: 2.8 Å EMDB-38976: WN353 bound APLNR complex 手法: EM (単粒子) / 解像度: 2.9 Å EMDB-38977: The focused refinement map (Receptor) of WN561 bound APLNR-Gi1 structure. 手法: EM (単粒子) / 解像度: 3.0 Å EMDB-38978: The focused refinement map (G-protein) of WN561 bound APLNR-Gi1 structure 手法: EM (単粒子) / 解像度: 2.8 Å EMDB-38979: WN561 bound APLNR complex 手法: EM (単粒子) / 解像度: 2.9 Å
化合物	PDB-1d5n: CRYSTAL STRUCTURE OF E. COLI MNSOD AT 100K
由来	homo sapiens (ヒト) synthetic construct (人工物)
キーワード	MEMBRANE PROTEIN / APLNR / Class A GPCR / Synthetic peptide / apelin / Structural protein / MM07 / Cyclic peptide / CMF-019 / G-protein-biased small molecule agonist