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	The dynamic basis of G-protein recognition and activation by a GPCR.
ジャーナル・号・ページ	Nature, Vol. 652, Issue 8110, Page 812-821, Year 2026
掲載日	2026年3月11日
著者	Kazuhiro Kobayashi / Kouki Kawakami / Toshiki E Matsui / Shun Yokoi / Masahiro Fukuda / Tomohiro J Narita / Hiroki Arai / Mai Tambo / Takashi Sumikama / Manae Tatsumi / Keitaro Yamashita / Junki Koyanagi / Mai Kugawa / Hisako Ikeda / Ayumi Sumino / Ayori Mitsutake / Brian K Kobilka / Asuka Inoue / Hideaki E Kato /
PubMed 要旨	G-protein-coupled receptor (GPCR) signalling occurs through heterotrimeric G proteins, whose selective activation leads to distinct cellular outcomes. Although more than 200 GPCR-G protein complex ...G-protein-coupled receptor (GPCR) signalling occurs through heterotrimeric G proteins, whose selective activation leads to distinct cellular outcomes. Although more than 200 GPCR-G protein complex structures have been determined, these static snapshots provide limited insight into the dynamics of G-protein association and dissociation. Here we present cryo-electron microscopy structures of human neurotensin receptor type 1 (NTSR1) with minimally modified G and G, showing how the receptor's intracellular surface dynamically rearranges to accommodate each G-protein subtype. Furthermore, time-resolved cryo-electron microscopy analyses of NTSR1-G visualized G-protein dissociation processes on GDP/GTP binding. Characterization of more than 20 intermediates, complemented by mutational and computational analyses, identifies four key mechanistic features. First, GDP/GTP induces G release from both canonical and non-canonical active conformations with distinct kinetics. Second, NTSR1 uses common intracellular rearrangements to recognize different G-protein subtypes and to promote activation of a single subtype. Third, separation from Gβγ involves stepwise remodelling of the Gα switches I-III. Finally, G dissociates from the receptor through a pathway that is distinct from that of G, and the canonical and non-canonical NTSR1-G complexes further diverge in their dissociation trajectories. These findings provide a comprehensive framework for understanding GPCR signalling dynamics and guiding signal-targeted therapeutic development.
リンク	Nature / PubMed:41813902
手法	EM (単粒子)
解像度	2.24 - 3.65 Å
構造データ	64904 9vat EMDB-64904, PDB-9vat: Cryo-EM structure of human Neurotensin Receptor 1 (hNTSR1)-Go complex in nucleotide-free C state 手法: EM (単粒子) / 解像度: 3.37 Å 64905 9vau EMDB-64905, PDB-9vau: Cryo-EM structure of human Neurotensin Receptor 1 (hNTSR1)-Go complex in nucleotide-free NC state 1 手法: EM (単粒子) / 解像度: 2.95 Å 64906 9vav EMDB-64906, PDB-9vav: Cryo-EM structure of human Neurotensin Receptor 1 (hNTSR1)-Go complex in nucleotide-free NC state 2 手法: EM (単粒子) / 解像度: 2.99 Å 64907 9vaw EMDB-64907, PDB-9vaw: Cryo-EM structure of human Neurotensin Receptor 1 (hNTSR1)-Gq (delipidated) complex in nucleotide-free C state 手法: EM (単粒子) / 解像度: 2.24 Å 64908 9vax EMDB-64908, PDB-9vax: Cryo-EM structure of human Neurotensin Receptor 1 (hNTSR1)-Gi1 complex in nucleotide-free C state 1 手法: EM (単粒子) / 解像度: 3.46 Å 64909 9vay EMDB-64909, PDB-9vay: Cryo-EM structure of human Neurotensin Receptor 1 (hNTSR1)-Gi1 complex in nucleotide-free C state 2 手法: EM (単粒子) / 解像度: 3.65 Å 64910 9vaz EMDB-64910, PDB-9vaz: Cryo-EM structure of human Neurotensin Receptor 1 (hNTSR1)-Gi1 complex in nucleotide-free NC state 1 手法: EM (単粒子) / 解像度: 3.38 Å 64911 9vb0 EMDB-64911, PDB-9vb0: Cryo-EM structure of human Neurotensin Receptor 1 (hNTSR1)-Gi1 complex in nucleotide-free NC state 2 手法: EM (単粒子) / 解像度: 3.19 Å 64912 9vb1 EMDB-64912, PDB-9vb1: Cryo-EM structure of human Neurotensin Receptor 1 (hNTSR1)-Gi1 complex in nucleotide-free NC state 3 手法: EM (単粒子) / 解像度: 3.31 Å 64913 9vb2 EMDB-64913, PDB-9vb2: Cryo-EM structure of the human neurotensin receptor 1 (hNTSR1)-Gi1 complex in the GDP-bound, AHD-closed C state 1, plunge-frozen 8 seconds after GDP addition 手法: EM (単粒子) / 解像度: 3.08 Å 64914 9vb3 EMDB-64914, PDB-9vb3: Cryo-EM structure of the human neurotensin receptor 1 (hNTSR1)-Gi1 complex in the GDP-bound, AHD-closed C state 2, plunge-frozen 8 seconds after GDP addition 手法: EM (単粒子) / 解像度: 3.02 Å 64915 9vb4 EMDB-64915, PDB-9vb4: Cryo-EM structure of the human neurotensin receptor 1 (hNTSR1)-Gi1 complex in the GDP-bound, AHD-closed C state 1, plunge-frozen 15 seconds after GDP addition 手法: EM (単粒子) / 解像度: 2.85 Å 64916 9vb5 EMDB-64916, PDB-9vb5: Cryo-EM structure of the human neurotensin receptor 1 (hNTSR1)-Gi1 complex in the GDP-bound, AHD-closed C state 2, plunge-frozen 15 seconds after GDP addition 手法: EM (単粒子) / 解像度: 3.14 Å 64917 9vb6 EMDB-64917, PDB-9vb6: Cryo-EM structure of the human neurotensin receptor 1 (hNTSR1)-Gi1 complex in the GTP-bound, AHD-open C state, plunge-frozen 8 seconds after GTP addition 手法: EM (単粒子) / 解像度: 3.38 Å 64918 9vb7 EMDB-64918, PDB-9vb7: Cryo-EM structure of the human neurotensin receptor 1 (hNTSR1)-Gi1 complex in the GTP-bound, AHD-closed C state 1, plunge-frozen 8 seconds after GTP addition 手法: EM (単粒子) / 解像度: 3.01 Å 64919 9vba EMDB-64919, PDB-9vba: Cryo-EM structure of the human neurotensin receptor 1 (hNTSR1)-Gi1 complex in the GTP-bound, AHD-closed C state 2, plunge-frozen 8 seconds after GTP addition 手法: EM (単粒子) / 解像度: 3.38 Å 67426 20zc EMDB-67426, PDB-20zc: Cryo-EM structure of human Neurotensin Receptor 1 (hNTSR1)-Gi1 (delipidated) complex in nucleotide-free C state 手法: EM (単粒子) / 解像度: 2.6 Å 67427 20zd EMDB-67427, PDB-20zd: Cryo-EM structure of human Neurotensin Receptor 1 (hNTSR1)-Gi1 (delipidated) complex in nucleotide-free NC state 手法: EM (単粒子) / 解像度: 2.8 Å 67429 20zg EMDB-67429, PDB-20zg: Cryo-EM structure of the human neurotensin receptor 1 (hNTSR1)-Gi1 complex in the GTP-bound, AHD-open C state 1, plunge-frozen 0-5 seconds after GTP addition 手法: EM (単粒子) / 解像度: 2.4 Å 67430 20zh EMDB-67430, PDB-20zh: Cryo-EM structure of the human neurotensin receptor 1 (hNTSR1)-Gi1 complex in the GTP-bound, AHD-open C state 2, plunge-frozen 0-5 seconds after GTP addition 手法: EM (単粒子) / 解像度: 2.4 Å 67431 20zi EMDB-67431, PDB-20zi: Cryo-EM structure of the human neurotensin receptor 1 (hNTSR1)-Gi1 complex in the GTP-bound, AHD-open NC state 1, plunge-frozen 0-5 seconds after GTP addition 手法: EM (単粒子) / 解像度: 2.7 Å 67432 20zj EMDB-67432, PDB-20zj: Cryo-EM structure of the human neurotensin receptor 1 (hNTSR1)-Gi1 complex in the GTP-bound, AHD-open NC state 2, plunge-frozen 0-5 seconds after GTP addition 手法: EM (単粒子) / 解像度: 2.9 Å 67433 20zk EMDB-67433, PDB-20zk: Cryo-EM structure of the human neurotensin receptor 1 (hNTSR1)-Gi1 complex in the GTP-bound, AHD-open NC state 3, plunge-frozen 0-5 seconds after GTP addition 手法: EM (単粒子) / 解像度: 2.7 Å 67434 20zl EMDB-67434, PDB-20zl: Cryo-EM structure of the human neurotensin receptor 1 (hNTSR1)-Gi1 complex in the GTP-bound, AHD-open NC state 4, plunge-frozen 0-5 seconds after GTP addition 手法: EM (単粒子) / 解像度: 3.1 Å
化合物	ChemComp-GTP: GUANOSINE-5'-TRIPHOSPHATE / GTP, エネルギー貯蔵分子YM ChemComp-HOH: WATER ChemComp-GDP: GUANOSINE-5'-DIPHOSPHATE / GDP, エネルギー貯蔵分子YM ChemComp-MG: Unknown entry
由来	homo sapiens (ヒト) synthetic construct (人工物) mus musculus (ハツカネズミ)
キーワード	MEMBRANE PROTEIN / GPCR / NTSR1 / neurotensin / G-protein