9vb4: Difference between revisions
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==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== | |||
<StructureSection load='9vb4' size='340' side='right'caption='[[9vb4]], [[Resolution|resolution]] 2.85Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[9vb4]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9VB4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9VB4 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.85Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9vb4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9vb4 OCA], [https://pdbe.org/9vb4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9vb4 RCSB], [https://www.ebi.ac.uk/pdbsum/9vb4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9vb4 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/NTR1_HUMAN NTR1_HUMAN] Receptor for the tridecapeptide neurotensin. It is associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
G-protein-coupled receptor (GPCR) signalling occurs through heterotrimeric G proteins, whose selective activation leads to distinct cellular outcomes(1). Although more than 200 GPCR-G protein complex structures have been determined(2), 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(o) and G(q), 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(i) 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(i) 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 Gbetagamma involves stepwise remodelling of the Galpha switches I-III. Finally, G(i) dissociates from the receptor through a pathway that is distinct from that of G(s), and the canonical and non-canonical NTSR1-G(i) complexes further diverge in their dissociation trajectories. These findings provide a comprehensive framework for understanding GPCR signalling dynamics and guiding signal-targeted therapeutic development. | |||
The dynamic basis of G-protein recognition and activation by a GPCR.,Kobayashi K, Kawakami K, Matsui TE, Yokoi S, Fukuda M, Narita TJ, Arai H, Tambo M, Sumikama T, Tatsumi M, Yamashita K, Koyanagi J, Kugawa M, Ikeda H, Sumino A, Mitsutake A, Kobilka BK, Inoue A, Kato HE Nature. 2026 Apr;652(8110):812-821. doi: 10.1038/s41586-026-10228-w. Epub 2026 , Mar 11. PMID:41813902<ref>PMID:41813902</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 9vb4" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | |||
[[Category: Synthetic construct]] | |||
[[Category: Fukuda M]] | |||
[[Category: Kato HE]] | |||
[[Category: Kawakami K]] | |||
[[Category: Kobayashi K]] | |||
[[Category: Matsui TE]] | |||
[[Category: Yamashita K]] | |||
