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| | <StructureSection load='6m8s' size='340' side='right'caption='[[6m8s]], [[Resolution|resolution]] 3.71Å' scene=''> | | <StructureSection load='6m8s' size='340' side='right'caption='[[6m8s]], [[Resolution|resolution]] 3.71Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6m8s]] is a 15 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=6M8S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6M8S FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6m8s]] is a 15 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=6M8S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6M8S FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6m8r|6m8r]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.71Å</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]), KCTD12, C13orf2, KIAA1778, PFET1 ([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'>[https://proteopedia.org/fgij/fg.htm?mol=6m8s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6m8s OCA], [https://pdbe.org/6m8s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6m8s RCSB], [https://www.ebi.ac.uk/pdbsum/6m8s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6m8s ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6m8s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6m8s OCA], [http://pdbe.org/6m8s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6m8s RCSB], [http://www.ebi.ac.uk/pdbsum/6m8s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6m8s ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[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/KCD12_HUMAN KCD12_HUMAN]] Auxiliary subunit of GABA-B receptors that determine the pharmacology and kinetics of the receptor response. Increases agonist potency and markedly alter the G-protein signaling of the receptors by accelerating onset and promoting desensitization (By similarity). [[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). | + | [https://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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6m8s" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6m8s" 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 == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Kruse, A C]] | + | [[Category: Kruse AC]] |
| - | [[Category: Zheng, S]] | + | [[Category: Zheng S]] |
| - | [[Category: Beta-propeller]]
| + | |
| - | [[Category: Gabab desensitization]]
| + | |
| - | [[Category: Homopentamer]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Function
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]
Publication Abstract from PubMed
The GABAB (gamma-aminobutyric acid type B) receptor is one of the principal inhibitory neurotransmitter receptors in the brain, and it signals through heterotrimeric G proteins to activate a variety of effectors, including G-protein-coupled inwardly rectifying potassium channels (GIRKs)(1,2). GABAB-receptor signalling is tightly regulated by auxiliary subunits called KCTDs, which control the kinetics of GIRK activation and desensitization(3-5). However, the mechanistic basis for KCTD modulation of GABAB signalling remains incompletely understood. Here, using a combination of X-ray crystallography, electron microscopy, and functional and biochemical experiments, we reveal the molecular details of KCTD binding to both GABAB receptors and G-protein betagamma subunits. KCTDs associate with the receptor by forming an asymmetric pentameric ring around a region of the receptor carboxy-terminal tail, while a second KCTD domain, H1, engages in a symmetric interaction with five copies of Gbetagamma in which the G-protein subunits also interact directly with one another. We further show that KCTD binding to Gbetagamma is highly cooperative, defining a model in which KCTD proteins cooperatively strip G proteins from GIRK channels to induce rapid desensitization following receptor activation. These results provide a framework for understanding the molecular basis for the precise temporal control of GABAB signalling by KCTD proteins.
Structural basis for KCTD-mediated rapid desensitization of GABAB signalling.,Zheng S, Abreu N, Levitz J, Kruse AC Nature. 2019 Mar;567(7746):127-131. doi: 10.1038/s41586-019-0990-0. Epub 2019 Feb, 27. PMID:30814734[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
- ↑ Zheng S, Abreu N, Levitz J, Kruse AC. Structural basis for KCTD-mediated rapid desensitization of GABAB signalling. Nature. 2019 Mar;567(7746):127-131. doi: 10.1038/s41586-019-0990-0. Epub 2019 Feb, 27. PMID:30814734 doi:http://dx.doi.org/10.1038/s41586-019-0990-0
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