View source for 8tzq


==CryoEM structure of D2 dopamine receptor in complex with GoA KE Mutant, scFv16, and dopamine==
<StructureSection load='8tzq' size='340' side='right'caption='[[8tzq]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8tzq]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8TZQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8TZQ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.2&#8491;</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=8tzq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8tzq OCA], [https://pdbe.org/8tzq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8tzq RCSB], [https://www.ebi.ac.uk/pdbsum/8tzq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8tzq ProSAT]</span></td></tr>
</table>
== Function ==
[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;">
== Publication Abstract from PubMed ==
Many neurotransmitter receptors activate G proteins through exchange of GDP for GTP. The intermediate nucleotide-free state has eluded characterization, due largely to its inherent instability. Here we characterize a G protein variant associated with a rare neurological disorder in humans. Galpha(o)(K46E) has a charge reversal that clashes with the phosphate groups of GDP and GTP. As anticipated, the purified protein binds poorly to guanine nucleotides yet retains wild-type affinity for G protein betagamma subunits. In cells with physiological concentrations of nucleotide, Galpha(o)(K46E) forms a stable complex with receptors and Gbetagamma, impeding effector activation. Further, we demonstrate that the mutant can be easily purified in complex with dopamine-bound D2 receptors, and use cryo-electron microscopy to determine the structure, including both domains of Galpha(o), without nucleotide or stabilizing nanobodies. These findings reveal the molecular basis for the first committed step of G protein activation, establish a mechanistic basis for a neurological disorder, provide a simplified strategy to determine receptor-G protein structures, and a method to detect high affinity agonist binding in cells.

A neurodevelopmental disorder mutation locks G proteins in the transitory pre-activated state.,Knight KM, Krumm BE, Kapolka NJ, Ludlam WG, Cui M, Mani S, Prytkova I, Obarow EG, Lefevre TJ, Wei W, Ma N, Huang XP, Fay JF, Vaidehi N, Smrcka AV, Slesinger PA, Logothetis DE, Martemyanov KA, Roth BL, Dohlman HG Nat Commun. 2024 Aug 5;15(1):6643. doi: 10.1038/s41467-024-50964-z. PMID:39103320<ref>PMID:39103320</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8tzq" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Fay JF]]
[[Category: Kapolka NJ]]
[[Category: Krumm BE]]
[[Category: Roth BL]]