6b20: Difference between revisions
New page: '''Unreleased structure''' The entry 6b20 is ON HOLD until Paper Publication Authors: Gulati, S., Kiser, P.D., Palczewski, K. Description: Crystal structure of a complex between G prot... |
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==Crystal structure of a complex between G protein beta gamma dimer and an inhibitory Nanobody regulator== | |||
<StructureSection load='6b20' size='340' side='right'caption='[[6b20]], [[Resolution|resolution]] 2.34Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6b20]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B20 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6B20 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.34Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></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=6b20 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b20 OCA], [https://pdbe.org/6b20 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6b20 RCSB], [https://www.ebi.ac.uk/pdbsum/6b20 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6b20 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/GBG1_BOVIN GBG1_BOVIN] 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. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
G protein-coupled receptors (GPCRs) activate heterotrimeric G proteins by mediating a GDP to GTP exchange in the Galpha subunit. This leads to dissociation of the heterotrimer into Galpha-GTP and Gbetagamma dimer. The Galpha-GTP and Gbetagamma dimer each regulate a variety of downstream pathways to control various aspects of human physiology. Dysregulated Gbetagamma-signaling is a central element of various neurological and cancer-related anomalies. However, Gbetagamma also serves as a negative regulator of Galpha that is essential for G protein inactivation, and thus has the potential for numerous side effects when targeted therapeutically. Here we report a llama-derived nanobody (Nb5) that binds tightly to the Gbetagamma dimer. Nb5 responds to all combinations of beta-subtypes and gamma-subtypes and competes with other Gbetagamma-regulatory proteins for a common binding site on the Gbetagamma dimer. Despite its inhibitory effect on Gbetagamma-mediated signaling, Nb5 has no effect on Galphaq-mediated and Galphas-mediated signaling events in living cells. | |||
Targeting G protein-coupled receptor signaling at the G protein level with a selective nanobody inhibitor.,Gulati S, Jin H, Masuho I, Orban T, Cai Y, Pardon E, Martemyanov KA, Kiser PD, Stewart PL, Ford CP, Steyaert J, Palczewski K Nat Commun. 2018 May 18;9(1):1996. doi: 10.1038/s41467-018-04432-0. PMID:29777099<ref>PMID:29777099</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Gulati | <div class="pdbe-citations 6b20" style="background-color:#fffaf0;"></div> | ||
[[Category: Kiser | |||
[[Category: Palczewski | ==See Also== | ||
*[[GTP-binding protein 3D structures|GTP-binding protein 3D structures]] | |||
*[[Transducin 3D structures|Transducin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Bos taurus]] | |||
[[Category: Lama glama]] | |||
[[Category: Large Structures]] | |||
[[Category: Gulati S]] | |||
[[Category: Kiser PD]] | |||
[[Category: Palczewski K]] | |||
Latest revision as of 10:49, 17 October 2024
Crystal structure of a complex between G protein beta gamma dimer and an inhibitory Nanobody regulatorCrystal structure of a complex between G protein beta gamma dimer and an inhibitory Nanobody regulator
Structural highlights
FunctionGBG1_BOVIN 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. Publication Abstract from PubMedG protein-coupled receptors (GPCRs) activate heterotrimeric G proteins by mediating a GDP to GTP exchange in the Galpha subunit. This leads to dissociation of the heterotrimer into Galpha-GTP and Gbetagamma dimer. The Galpha-GTP and Gbetagamma dimer each regulate a variety of downstream pathways to control various aspects of human physiology. Dysregulated Gbetagamma-signaling is a central element of various neurological and cancer-related anomalies. However, Gbetagamma also serves as a negative regulator of Galpha that is essential for G protein inactivation, and thus has the potential for numerous side effects when targeted therapeutically. Here we report a llama-derived nanobody (Nb5) that binds tightly to the Gbetagamma dimer. Nb5 responds to all combinations of beta-subtypes and gamma-subtypes and competes with other Gbetagamma-regulatory proteins for a common binding site on the Gbetagamma dimer. Despite its inhibitory effect on Gbetagamma-mediated signaling, Nb5 has no effect on Galphaq-mediated and Galphas-mediated signaling events in living cells. Targeting G protein-coupled receptor signaling at the G protein level with a selective nanobody inhibitor.,Gulati S, Jin H, Masuho I, Orban T, Cai Y, Pardon E, Martemyanov KA, Kiser PD, Stewart PL, Ford CP, Steyaert J, Palczewski K Nat Commun. 2018 May 18;9(1):1996. doi: 10.1038/s41467-018-04432-0. PMID:29777099[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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