7vgz
From Proteopedia
(Difference between revisions)
| (One intermediate revision not shown.) | |||
| Line 4: | Line 4: | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7vgz]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus], [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] 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=7VGZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7VGZ FirstGlance]. <br> | <table><tr><td colspan='2'>[[7vgz]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus], [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] 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=7VGZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7VGZ FirstGlance]. <br> | ||
| - | </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=JEV:N- | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.3Å</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=JEV:~{N}-[2-[(8~{S})-2,6,7,8-tetrahydro-1~{H}-cyclopenta[e][1]benzofuran-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=7vgz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7vgz OCA], [https://pdbe.org/7vgz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7vgz RCSB], [https://www.ebi.ac.uk/pdbsum/7vgz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7vgz 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=7vgz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7vgz OCA], [https://pdbe.org/7vgz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7vgz RCSB], [https://www.ebi.ac.uk/pdbsum/7vgz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7vgz ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
| - | + | [https://www.uniprot.org/uniprot/MTR1A_HUMAN MTR1A_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> | ||
Current revision
MT1-remalteon-Gi complex
| |||||||||||
