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==== | ==Cryo-EM structure of histamine H1 receptor Gq complex== | ||
<StructureSection load='7dfl' size='340' side='right'caption='[[7dfl]]' scene=''> | <StructureSection load='7dfl' size='340' side='right'caption='[[7dfl]], [[Resolution|resolution]] 3.30Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | <table><tr><td colspan='2'>[[7dfl]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7DFL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7DFL FirstGlance]. <br> | ||
</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=7dfl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7dfl OCA], [https://pdbe.org/7dfl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7dfl RCSB], [https://www.ebi.ac.uk/pdbsum/7dfl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7dfl ProSAT]</span></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]] 3.3Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HSM:HISTAMINE'>HSM</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=7dfl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7dfl OCA], [https://pdbe.org/7dfl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7dfl RCSB], [https://www.ebi.ac.uk/pdbsum/7dfl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7dfl ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/HRH1_HUMAN HRH1_HUMAN] In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Histamine receptors play important roles in various pathophysiological conditions and are effective targets for anti-allergy treatment, however the mechanism of receptor activation remain elusive. Here, we present the cryo-electron microscopy (cryo-EM) structure of the human H(1)R in complex with a G(q) protein in an active conformation via a NanoBiT tethering strategy. The structure reveals that histamine activates receptor via interacting with the key residues of both transmembrane domain 3 (TM3) and TM6 to squash the binding pocket on the extracellular side and to open the cavity on the intracellular side for G(q) engagement in a model of "squash to activate and expand to deactivate". The structure also reveals features for G(q) coupling, including the interaction between intracellular loop 2 (ICL2) and the alphaN-beta junction of G(q/11) protein. The detailed analysis of our structure will provide a framework for understanding G-protein coupling selectivity and clues for designing novel antihistamines. | |||
Cryo-EM structure of the human histamine H(1) receptor/G(q) complex.,Xia R, Wang N, Xu Z, Lu Y, Song J, Zhang A, Guo C, He Y Nat Commun. 2021 Apr 7;12(1):2086. doi: 10.1038/s41467-021-22427-2. PMID:33828102<ref>PMID:33828102</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7dfl" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[GTP-binding protein 3D structures|GTP-binding protein 3D structures]] | |||
*[[Transducin 3D structures|Transducin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Z | [[Category: He Y]] | ||
[[Category: Wang N]] | |||
[[Category: Xia R]] | |||
[[Category: Xu Z]] | |||
Latest revision as of 09:12, 21 November 2024
Cryo-EM structure of histamine H1 receptor Gq complexCryo-EM structure of histamine H1 receptor Gq complex
Structural highlights
FunctionHRH1_HUMAN In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system. Publication Abstract from PubMedHistamine receptors play important roles in various pathophysiological conditions and are effective targets for anti-allergy treatment, however the mechanism of receptor activation remain elusive. Here, we present the cryo-electron microscopy (cryo-EM) structure of the human H(1)R in complex with a G(q) protein in an active conformation via a NanoBiT tethering strategy. The structure reveals that histamine activates receptor via interacting with the key residues of both transmembrane domain 3 (TM3) and TM6 to squash the binding pocket on the extracellular side and to open the cavity on the intracellular side for G(q) engagement in a model of "squash to activate and expand to deactivate". The structure also reveals features for G(q) coupling, including the interaction between intracellular loop 2 (ICL2) and the alphaN-beta junction of G(q/11) protein. The detailed analysis of our structure will provide a framework for understanding G-protein coupling selectivity and clues for designing novel antihistamines. Cryo-EM structure of the human histamine H(1) receptor/G(q) complex.,Xia R, Wang N, Xu Z, Lu Y, Song J, Zhang A, Guo C, He Y Nat Commun. 2021 Apr 7;12(1):2086. doi: 10.1038/s41467-021-22427-2. PMID:33828102[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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