7vh0
From Proteopedia
(Difference between revisions)
| Line 4: | Line 4: | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7vh0]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7VH0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7VH0 FirstGlance]. <br> | <table><tr><td colspan='2'>[[7vh0]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7VH0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7VH0 FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=JEV:N-{2-[(8S)-1,6,7,8-tetrahydro-2H-indeno[5,4-b]furan-8-yl]ethyl}propanamide'>JEV</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.46Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=JEV:N-{2-[(8S)-1,6,7,8-tetrahydro-2H-indeno[5,4-b]furan-8-yl]ethyl}propanamide'>JEV</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=7vh0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7vh0 OCA], [https://pdbe.org/7vh0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7vh0 RCSB], [https://www.ebi.ac.uk/pdbsum/7vh0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7vh0 ProSAT]</span></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=7vh0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7vh0 OCA], [https://pdbe.org/7vh0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7vh0 RCSB], [https://www.ebi.ac.uk/pdbsum/7vh0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7vh0 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
| - | + | [https://www.uniprot.org/uniprot/MTR1B_HUMAN MTR1B_HUMAN] High affinity receptor for melatonin. Likely to mediate the reproductive and circadian actions of melatonin. The activity of this receptor is mediated by pertussis toxin sensitive G proteins that inhibit adenylate cyclase activity. | |
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| - | Melatonin receptors ( | + | Melatonin receptors (MT(1) and MT(2) in humans) are family A G protein-coupled receptors that respond to the neurohormone melatonin to regulate circadian rhythm and sleep. Numerous efforts have been made to develop drugs targeting melatonin receptors for the treatment of insomnia, circadian rhythm disorder, and cancer. However, designing subtype-selective melatonergic drugs remains challenging. Here, we report the cryo-EM structures of the MT(1)-G(i) signaling complex with 2-iodomelatonin and ramelteon and the MT(2)-G(i) signaling complex with ramelteon. These structures, together with the reported functional data, reveal that although MT(1) and MT(2) possess highly similar orthosteric ligand-binding pockets, they also display distinctive features that could be targeted to design subtype-selective drugs. The unique structural motifs in MT(1) and MT(2) mediate structural rearrangements with a particularly wide opening on the cytoplasmic side. G(i) is engaged in the receptor core shared by MT(1) and MT(2) and presents a conformation deviating from those in other G(i) complexes. Together, our results provide new clues for designing melatonergic drugs and further insights into understanding the G protein coupling mechanism. |
Structural basis of the ligand binding and signaling mechanism of melatonin receptors.,Wang Q, Lu Q, Guo Q, Teng M, Gong Q, Li X, Du Y, Liu Z, Tao Y Nat Commun. 2022 Jan 24;13(1):454. doi: 10.1038/s41467-022-28111-3. PMID:35075127<ref>PMID:35075127</ref> | Structural basis of the ligand binding and signaling mechanism of melatonin receptors.,Wang Q, Lu Q, Guo Q, Teng M, Gong Q, Li X, Du Y, Liu Z, Tao Y Nat Commun. 2022 Jan 24;13(1):454. doi: 10.1038/s41467-022-28111-3. PMID:35075127<ref>PMID:35075127</ref> | ||
Revision as of 14:08, 6 November 2024
MT2-remalteon-Gi complex
| |||||||||||
