View source for 6g79


==Coupling specificity of heterotrimeric Go to the serotonin 5-HT1B receptor==
<SX load='6g79' size='340' side='right' viewer='molstar' caption='[[6g79]], [[Resolution|resolution]] 3.78&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6g79]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6G79 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6G79 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EP5:2-[5-[2-[4-(4-cyanophenyl)piperazin-1-yl]-2-oxidanylidene-ethoxy]-1~{H}-indol-3-yl]ethylazanium'>EP5</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GNB1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), GNG2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), GNAO1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), HTR1B, HTR1DB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6g79 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6g79 OCA], [http://pdbe.org/6g79 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6g79 RCSB], [http://www.ebi.ac.uk/pdbsum/6g79 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6g79 ProSAT]</span></td></tr>
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== Disease ==
[[http://www.uniprot.org/uniprot/GNAO_HUMAN GNAO_HUMAN]] Early infantile epileptic encephalopathy. The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry. 
== Function ==
[[http://www.uniprot.org/uniprot/5HT1B_HUMAN 5HT1B_HUMAN]] This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase activity. [[http://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>  [[http://www.uniprot.org/uniprot/GNAO_HUMAN GNAO_HUMAN]] Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(o) protein function is not clear. Stimulated by RGS14. [[http://www.uniprot.org/uniprot/GBG2_HUMAN GBG2_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 (By similarity). 
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== Publication Abstract from PubMed ==
G-protein-coupled receptors (GPCRs) form the largest family of receptors encoded by the human genome (around 800 genes). They transduce signals by coupling to a small number of heterotrimeric G proteins (16 genes encoding different alpha-subunits). Each human cell contains several GPCRs and G proteins. The structural determinants of coupling of Gs to four different GPCRs have been elucidated(1-4), but the molecular details of how the other G-protein classes couple to GPCRs are unknown. Here we present the cryo-electron microscopy structure of the serotonin 5-HT1B receptor (5-HT1BR) bound to the agonist donitriptan and coupled to an engineered Go heterotrimer. In this complex, 5-HT1BR is in an active state; the intracellular domain of the receptor is in a similar conformation to that observed for the beta2-adrenoceptor (beta2AR) (3) or the adenosine A2A receptor (A2AR) (1) in complex with Gs. In contrast to the complexes with Gs, the gap between the receptor and the Gbeta-subunit in the Go-5-HT1BR complex precludes molecular contacts, and the interface between the Galpha-subunit of Go and the receptor is considerably smaller. These differences are likely to be caused by the differences in the interactions with the C terminus of the Go alpha-subunit. The molecular variations between the interfaces of Go and Gs in complex with GPCRs may contribute substantially to both the specificity of coupling and the kinetics of signalling.

Cryo-EM structure of the serotonin 5-HT1B receptor coupled to heterotrimeric Go.,Garcia-Nafria J, Nehme R, Edwards PC, Tate CG Nature. 2018 Jun;558(7711):620-623. doi: 10.1038/s41586-018-0241-9. Epub 2018 Jun, 20. PMID:29925951<ref>PMID:29925951</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6g79" style="background-color:#fffaf0;"></div>

==See Also==
*[[Transducin 3D structures|Transducin 3D structures]]
*[[5-hydroxytryptamine receptor 3D structures|5-hydroxytryptamine receptor 3D structures]]
== References ==
<references/>
__TOC__
</SX>
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Edwards, P]]
[[Category: Garcia-Nafria, J]]
[[Category: Nehme, R]]
[[Category: Tate, C G]]
[[Category: 5-ht1b]]
[[Category: G-protein coupled receptor]]
[[Category: Membrane protein]]
[[Category: Mini-go]]
[[Category: Serotonin]]