View source for 21ag


==LY334370-bound serotonin 1F (5-HT1F) receptor-miniGoA protein complex==
<StructureSection load='21ag' size='340' side='right'caption='[[21ag]], [[Resolution|resolution]] 3.13&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[21ag]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=21AG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=21AG 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]] 3.13&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1E2G:4-fluoranyl-~{N}-[3-(1-methylpiperidin-4-yl)-1~{H}-indol-5-yl]benzamide'>A1E2G</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=21ag FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=21ag OCA], [https://pdbe.org/21ag PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=21ag RCSB], [https://www.ebi.ac.uk/pdbsum/21ag PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=21ag 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 ==
The 5-HT(1F) receptor is a serotonin receptor subtype highly expressed in trigeminal sensory neurons, where it modulates neuropeptide release and nociceptive signaling without inducing vasoconstriction. This makes it an important therapeutic target for migraine. LY334370 was developed as a first-generation selective 5-HT(1F)R agonist and demonstrated efficacy in clinical studies. However, the molecular mechanism underlying 5-HT(1F)R activation by LY334370 remains poorly understood. Here, we determined a 3.13 A cryo-EM structure of the LY334370-bound 5-HT(1F)R-miniGalpha(oA) complex. Combined with functional analyses, this structure delineates the molecular determinants underlying LY334370 recognition. Comparison with BRL54443 indicates that LY334370 selectivity for 5-HT(1F)R is driven by its optimal accommodation within the receptor-specific extended binding pocket. Furthermore, comparative analysis with the lasmiditan-bound 5-HT(1F)R-Galpha(i1) complex reveals distinct agonist binding modes and provides mechanistic insight into Galpha(i/o) subtype-specific coupling. Collectively, these findings elucidate the structural basis of 5-HT(1F)R activation, ligand selectivity, and G protein coupling, providing a structural framework for the rational design of safer and more effective anti-migraine drugs.

Structural basis of LY334370 recognition and selectivity at the 5-HT(1F) receptor.,Wang Y, Wang C, Cao C Biochem Biophys Res Commun. 2026 Mar 12;804:153313. doi: , 10.1016/j.bbrc.2026.153313. Epub 2026 Jan 21. PMID:41619505<ref>PMID:41619505</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 21ag" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Cao C]]
[[Category: Ji Z]]
[[Category: Wang Y]]