|
|
| Line 3: |
Line 3: |
| | <StructureSection load='5kdl' size='340' side='right'caption='[[5kdl]], [[Resolution|resolution]] 2.67Å' scene=''> | | <StructureSection load='5kdl' size='340' side='right'caption='[[5kdl]], [[Resolution|resolution]] 2.67Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5kdl]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KDL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KDL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5kdl]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KDL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5KDL FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GSP:5-GUANOSINE-DIPHOSPHATE-MONOTHIOPHOSPHATE'>GSP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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]] 2.665Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5kdo|5kdo]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GSP:5-GUANOSINE-DIPHOSPHATE-MONOTHIOPHOSPHATE'>GSP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Gnai1, Gnai-1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</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=5kdl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kdl OCA], [https://pdbe.org/5kdl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5kdl RCSB], [https://www.ebi.ac.uk/pdbsum/5kdl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5kdl 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=5kdl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kdl OCA], [http://pdbe.org/5kdl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kdl RCSB], [http://www.ebi.ac.uk/pdbsum/5kdl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kdl ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GNAI1_RAT GNAI1_RAT]] Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(i) proteins are involved in hormonal regulation of adenylate cyclase: they inhibit the cyclase in response to beta-adrenergic stimuli. The inactive GDP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division.<ref>PMID:16870394</ref> | + | [https://www.uniprot.org/uniprot/GNAI1_RAT GNAI1_RAT] Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(i) proteins are involved in hormonal regulation of adenylate cyclase: they inhibit the cyclase in response to beta-adrenergic stimuli. The inactive GDP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division.<ref>PMID:16870394</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 24: |
Line 23: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Buffalo rat]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Gilbert, J]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Hamm, H E]] | + | [[Category: Gilbert J]] |
| - | [[Category: Iverson, T M]] | + | [[Category: Hamm HE]] |
| - | [[Category: Kaya, A I]] | + | [[Category: Iverson TM]] |
| - | [[Category: Lokits, A D]] | + | [[Category: Kaya AI]] |
| - | [[Category: Meiler, J]] | + | [[Category: Lokits AD]] |
| - | [[Category: Heterotrimeric g protein g protein coupled receptors g protein activation g protein structure gdp release]]
| + | [[Category: Meiler J]] |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Function
GNAI1_RAT Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(i) proteins are involved in hormonal regulation of adenylate cyclase: they inhibit the cyclase in response to beta-adrenergic stimuli. The inactive GDP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division.[1]
Publication Abstract from PubMed
G protein coupled receptor (GPCR) mediated heterotrimeric G protein activation is a major mode of signal transduction in the cell. Previously, we and other groups reported that the alpha 5 (alpha5) helix of Galphai1, especially the hydrophobic interactions in this region, plays a key role during nucleotide release and G protein activation. To further investigate the effect of this hydrophobic core, we disrupted it in Galphai1 by inserting 4 alanine amino acids into the alpha5 helix between residues Q333 and F334 (Ins4A). This extends the length of the alpha5 helix without disturbing the beta6-alpha5 loop interactions. This mutant has high basal nucleotide exchange activity, yet no receptor-mediated activation of nucleotide exchange. By using structural approaches, we show that this mutant loses critical hydrophobic interactions leading to significant rearrangements of side chain residues H57, F189, F191, and F336; it also disturbs the rotation of the alpha5 helix, and the pi-pi interaction between H57 and F189. In addition, the insertion mutant abolishes G protein release from the activated receptor after nucleotide binding. Our biochemical and computational data indicate that the interactions between alpha5, alpha1 and beta2-beta3 are not only vital for GDP release during G protein activation, but they are also necessary for proper GTP binding (or GDP re-binding). Thus, our studies suggest that this hydrophobic interface is critical for accurate rearrangement of the alpha5 helix for G protein release from the receptor after GTP binding.
A conserved hydrophobic core in Galphai1 regulates G protein activation and release from activated receptor.,Kaya AI, Lokits AD, Gilbert JA, Iverson TM, Meiler J, Hamm HE J Biol Chem. 2016 Jul 26. pii: jbc.M116.745513. PMID:27462082[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Shu FJ, Ramineni S, Amyot W, Hepler JR. Selective interactions between Gi alpha1 and Gi alpha3 and the GoLoco/GPR domain of RGS14 influence its dynamic subcellular localization. Cell Signal. 2007 Jan;19(1):163-76. Epub 2006 Jul 25. PMID:16870394 doi:http://dx.doi.org/10.1016/j.cellsig.2006.06.002
- ↑ Kaya AI, Lokits AD, Gilbert JA, Iverson TM, Meiler J, Hamm HE. A conserved hydrophobic core in Galphai1 regulates G protein activation and release from activated receptor. J Biol Chem. 2016 Jul 26. pii: jbc.M116.745513. PMID:27462082 doi:http://dx.doi.org/10.1074/jbc.M116.745513
|
