6ukt: Difference between revisions

Latest revision as of 13:11, 6 November 2024

Cryo-EM structure of mammalian Ric-8A:Galpha(i):nanobody complex

Structural highlights

6ukt is a 6 chain structure with sequence from Lama glama and Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.87Å
Ligands:	SEP, TPO
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RIC8A_RAT Guanine nucleotide exchange factor (GEF), which can activate some, but not all, G-alpha proteins. Able to activate GNAI1, GNAO1 and GNAQ, but not GNAS by exchanging bound GDP for free GTP. Involved in regulation of microtubule pulling forces during mitotic movement of chromosomes by stimulating G(i)-alpha protein, possibly leading to release G(i)-alpha-GTP and NuMA proteins from the NuMA-GPSM2-G(i)-alpha-GDP complex. Also acts as an activator for G(q)-alpha (GNAQ) protein by enhancing the G(q)-coupled receptor-mediated ERK activation.^[1] ^[2]

Publication Abstract from PubMed

Ric-8A is a cytosolic Guanine Nucleotide exchange Factor (GEF) that activates heterotrimeric G protein alpha subunits (Galpha) and serves as an essential Galpha chaperone. Mechanisms by which Ric-8A catalyzes these activities, which are stimulated by Casein Kinase II phosphorylation, are unknown. We report the structure of the nanobody-stabilized complex of nucleotide-free Galpha bound to phosphorylated Ric-8A at near atomic resolution by cryo-electron microscopy and X-ray crystallography. The mechanism of Ric-8A GEF activity differs considerably from that employed by G protein-coupled receptors at the plasma membrane. Ric-8A engages a specific conformation of Galpha at multiple interfaces to form a complex that is stabilized by phosphorylation within a Ric-8A segment that connects two Galpha binding sites. The C-terminus of Galpha is ejected from its beta sheet core, thereby dismantling the GDP binding site. Ric-8A binds to the exposed Galpha beta sheet and switch II to stabilize the nucleotide-free state of Galpha.

Structure of the G protein chaperone and guanine nucleotide exchange factor Ric-8A bound to Galphai1.,McClelland LJ, Zhang K, Mou TC, Johnston J, Yates-Hansen C, Li S, Thomas CJ, Doukov TI, Triest S, Wohlkonig A, Tall GG, Steyaert J, Chiu W, Sprang SR Nat Commun. 2020 Feb 26;11(1):1077. doi: 10.1038/s41467-020-14943-4. PMID:32103024^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Tall GG, Krumins AM, Gilman AG. Mammalian Ric-8A (synembryn) is a heterotrimeric Galpha protein guanine nucleotide exchange factor. J Biol Chem. 2003 Mar 7;278(10):8356-62. PMID:12509430 doi:10.1074/jbc.M211862200
↑ Tall GG, Gilman AG. Resistance to inhibitors of cholinesterase 8A catalyzes release of Galphai-GTP and nuclear mitotic apparatus protein (NuMA) from NuMA/LGN/Galphai-GDP complexes. Proc Natl Acad Sci U S A. 2005 Nov 15;102(46):16584-9. PMID:16275912 doi:10.1073/pnas.0508306102
↑ McClelland LJ, Zhang K, Mou TC, Johnston J, Yates-Hansen C, Li S, Thomas CJ, Doukov TI, Triest S, Wohlkonig A, Tall GG, Steyaert J, Chiu W, Sprang SR. Structure of the G protein chaperone and guanine nucleotide exchange factor Ric-8A bound to Galphai1. Nat Commun. 2020 Feb 26;11(1):1077. doi: 10.1038/s41467-020-14943-4. PMID:32103024 doi:https://dx.doi.org/10.1038/s41467-020-14943-4

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Tall GG, Krumins AM, Gilman AG. Mammalian Ric-8A (synembryn) is a heterotrimeric Galpha protein guanine nucleotide exchange factor. J Biol Chem. 2003 Mar 7;278(10):8356-62. PMID:12509430 doi:10.1074/jbc.M211862200

[2] Tall GG, Gilman AG. Resistance to inhibitors of cholinesterase 8A catalyzes release of Galphai-GTP and nuclear mitotic apparatus protein (NuMA) from NuMA/LGN/Galphai-GDP complexes. Proc Natl Acad Sci U S A. 2005 Nov 15;102(46):16584-9. PMID:16275912 doi:10.1073/pnas.0508306102

[3] McClelland LJ, Zhang K, Mou TC, Johnston J, Yates-Hansen C, Li S, Thomas CJ, Doukov TI, Triest S, Wohlkonig A, Tall GG, Steyaert J, Chiu W, Sprang SR. Structure of the G protein chaperone and guanine nucleotide exchange factor Ric-8A bound to Galphai1. Nat Commun. 2020 Feb 26;11(1):1077. doi: 10.1038/s41467-020-14943-4. PMID:32103024 doi:https://dx.doi.org/10.1038/s41467-020-14943-4

[1]

[2]

[3]

@@ Line 3: / Line 3: @@
 <StructureSection load='6ukt' size='340' side='right'caption='[[6ukt]], [[Resolution|resolution]] 3.87&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6ukt]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UKT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6UKT FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6ukt]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Lama_glama Lama glama] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UKT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UKT FirstGlance]. <br>
-</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.87&#8491;</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=6ukt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ukt OCA], [http://pdbe.org/6ukt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ukt RCSB], [http://www.ebi.ac.uk/pdbsum/6ukt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ukt ProSAT]</span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</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=6ukt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ukt OCA], [https://pdbe.org/6ukt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ukt RCSB], [https://www.ebi.ac.uk/pdbsum/6ukt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ukt ProSAT]</span></td></tr>
 </table>
 == 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/RIC8A_RAT RIC8A_RAT] Guanine nucleotide exchange factor (GEF), which can activate some, but not all, G-alpha proteins. Able to activate GNAI1, GNAO1 and GNAQ, but not GNAS by exchanging bound GDP for free GTP. Involved in regulation of microtubule pulling forces during mitotic movement of chromosomes by stimulating G(i)-alpha protein, possibly leading to release G(i)-alpha-GTP and NuMA proteins from the NuMA-GPSM2-G(i)-alpha-GDP complex. Also acts as an activator for G(q)-alpha (GNAQ) protein by enhancing the G(q)-coupled receptor-mediated ERK activation.<ref>PMID:12509430</ref> <ref>PMID:16275912</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 18: / Line 19: @@
 </div>
 <div class="pdbe-citations 6ukt" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[GTP-binding protein 3D structures|GTP-binding protein 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Lama glama]]
 [[Category: Large Structures]]
-[[Category: Chiu, W]]
+[[Category: Rattus norvegicus]]
-[[Category: Johnston, J D]]
+[[Category: Chiu W]]
-[[Category: Mou, T C]]
+[[Category: Johnston JD]]
-[[Category: Sprang, S R]]
+[[Category: Mou TC]]
-[[Category: Zhang, K]]
+[[Category: Sprang SR]]
-[[Category: G protein]]
+[[Category: Zhang K]]
-[[Category: Gef]]
-[[Category: Ric-8a]]
-[[Category: Signaling protein]]

6ukt: Difference between revisions

Latest revision as of 13:11, 6 November 2024

Cryo-EM structure of mammalian Ric-8A:Galpha(i):nanobody complex

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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