View source for 9jmd


==Cryo-EM structure of the Azithromycin-Motilin receptor-Gq protein complex==
<StructureSection load='9jmd' size='340' side='right'caption='[[9jmd]], [[Resolution|resolution]] 2.74&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9jmd]] 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=9JMD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9JMD 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]] 2.74&#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>, <scene name='pdbligand=ZIT:AZITHROMYCIN'>ZIT</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=9jmd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9jmd OCA], [https://pdbe.org/9jmd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9jmd RCSB], [https://www.ebi.ac.uk/pdbsum/9jmd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9jmd 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 motilin receptor (MTLR) is a key target for treating gastrointestinal (GI) disorders like gastroparesis, yet developing effective agonists remains challenging due to drug tolerance and signaling bias. We present cryoelectron microscopy (cryo-EM) structures of MTLR bound to azithromycin, a macrolide antibiotic, and DS-3801b, a non-macrolide agonist. Distinct ligand recognition mechanisms are revealed, with azithromycin binding deeply within the orthosteric pocket and DS-3801b adopting a special clamp-like conformation stabilized by a water molecule. We also highlight the critical role of extracellular loop 2 (ECL2) in ligand specificity and signaling pathway activation, affecting both G-protein and beta-arrestin signaling. Additionally, the "D(2.60)R(2.63)S(3.28)" motif and interactions around transmembranes 6/7 (TM6/7) are identified as key drivers of signaling selectivity. These findings offer insights into the structural dynamics of MTLR, laying the groundwork for the rational design of next-generation GI prokinetic drugs with enhanced efficacy and safety.

Decoding the structural basis of ligand recognition and biased signaling in the motilin receptor.,You C, Jiang M, Gao T, Zhu Z, He X, Xu Y, Gao Y, Jiang Y, Xu HE Cell Rep. 2025 Mar 25;44(3):115329. doi: 10.1016/j.celrep.2025.115329. Epub 2025 , Feb 22. PMID:39987561<ref>PMID:39987561</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9jmd" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Jiang Y]]
[[Category: Xu HE]]
[[Category: You C]]