View source for 9vau


==Cryo-EM structure of human Neurotensin Receptor 1 (hNTSR1)-Go complex in nucleotide-free NC state 1==
<StructureSection load='9vau' size='340' side='right'caption='[[9vau]], [[Resolution|resolution]] 2.95&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9vau]] 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=9VAU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9VAU 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]] 2.95&#8491;</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=9vau FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9vau OCA], [https://pdbe.org/9vau PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9vau RCSB], [https://www.ebi.ac.uk/pdbsum/9vau PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9vau 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.
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== 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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 9vau" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</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]]