View source for 8zsj


==Cryo-EM structure of the apo hTAAR1-Gs complex==
<StructureSection load='8zsj' size='340' side='right'caption='[[8zsj]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8zsj]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli], [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8ZSJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8ZSJ 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]] 2.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</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=8zsj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8zsj OCA], [https://pdbe.org/8zsj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8zsj RCSB], [https://www.ebi.ac.uk/pdbsum/8zsj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8zsj ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GBB1_HUMAN GBB1_HUMAN] Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction.<ref>PMID:18611381</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Increasing global concerns about psychoactive substance addiction and psychotic disorders highlight the need for comprehensive research into the structure-function relationship governing ligand recognition between these substances and their receptors in the brain. Recent studies indicate the significant involvement of trace amine-associated receptor 1 (TAAR1) in the signaling regulation of the hallucinogen lysergic acid diethylamide (LSD) and other antipsychotic drugs. This study presents structures of the TAAR1-Gs protein complex recognizing LSD, which exhibits a polypharmacological profile, and the partial agonist RO5263397, which is a drug candidate for schizophrenia and addiction. Moreover, we elucidate the cross-species recognition and partial activation mechanism for TAAR1, which holds promising implications from a drug discovery perspective. Through mutagenesis, functional studies, and molecular dynamics (MD) simulations, we provide a comprehensive understanding of a versatile TAAR1 pocket in recognizing various ligands as well as in the ligand-free state, underpinning the structural basis of its high adaptability. These findings offer valuable insights for the design of antipsychotic drugs.

The versatile binding landscape of the TAAR1 pocket for LSD and other antipsychotic drug molecules.,Jiang K, Zheng Y, Zeng L, Wang L, Li F, Pu J, Lu Y, Zhao S, Xu F Cell Rep. 2024 Jul 11;43(7):114505. doi: 10.1016/j.celrep.2024.114505. PMID:39002128<ref>PMID:39002128</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8zsj" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Homo sapiens]]
[[Category: Lama glama]]
[[Category: Large Structures]]
[[Category: Jiang KX]]
[[Category: Xu F]]
[[Category: Zheng Y]]