Structural highlights
Disease
[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
[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. [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.[1] [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. [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).
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Johnston CA, Kimple AJ, Giguere PM, Siderovski DP. Structure of the parathyroid hormone receptor C terminus bound to the G-protein dimer Gbeta1gamma2. Structure. 2008 Jul;16(7):1086-94. PMID:18611381 doi:http://dx.doi.org/10.1016/j.str.2008.04.010
- ↑ Garcia-Nafria J, Nehme R, Edwards PC, Tate CG. Cryo-EM structure of the serotonin 5-HT1B receptor coupled to heterotrimeric Go. Nature. 2018 Jun;558(7711):620-623. doi: 10.1038/s41586-018-0241-9. Epub 2018 Jun, 20. PMID:29925951 doi:http://dx.doi.org/10.1038/s41586-018-0241-9
