8sta

From Proteopedia

(Difference between revisions)

Revision as of 05:32, 9 August 2023

Isobutyryl-CoA mutase fused in the presence of GMPPCP

Structural highlights

8sta is a 4 chain structure with sequence from Cupriavidus metallidurans CH34. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 7.3Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ICMF_CUPMC Catalyzes the reversible interconversion of isobutyryl-CoA and n-butyryl-CoA, and to a much lesser extent, of pivalyl-CoA and isovaleryl-CoA, using radical chemistry (PubMed:22167181). Also exhibits GTPase activity, associated with its G-protein domain (MeaI) that functions as a chaperone that assists cofactor delivery and proper holo-enzyme assembly (PubMed:22167181, PubMed:25675500). The G-domain of IcmF has also a role in its cofactor repair (PubMed:28130442). Does not display ATPase activity.^[1] ^[2] ^[3]

Publication Abstract from PubMed

G-protein metallochaperones are essential for the proper maturation of numerous metalloenzymes. The G-protein chaperone MMAA in humans (MeaB in bacteria) uses GTP hydrolysis to facilitate the delivery of adenosylcobalamin (AdoCbl) to AdoCbl-dependent methylmalonyl-CoA mutase, an essential metabolic enzyme. This G-protein chaperone also facilitates the removal of damaged cobalamin (Cbl) for repair. Although most chaperones are standalone proteins, IcmF (isobutyryl-CoA mutase fused) has a G-protein domain covalently attached to its target mutase. We previously showed that dimeric MeaB undergoes a 180 degrees rotation to reach a state capable of GTP hydrolysis (an active G-protein state), in which so-called switch III residues of one protomer contact the G-nucleotide of the other protomer. However, it was unclear whether other G-protein chaperones also adopted this conformation. Here we show that the G-protein domain in a fused system forms a similar active conformation, requiring IcmF oligomerization. IcmF oligomerizes both upon Cbl damage and in the presence of the nonhydrolyzable GTP analog, guanosine-5'-[(beta,gamma)-methyleno]triphosphate, forming supramolecular complexes observable by mass photometry and electron microscopy. Cryogenic electron microscopy (cryo-EM) structural analysis reveals that the second protomer of the G-protein intermolecular dimer props open the mutase active site using residues of switch III as a wedge, allowing for AdoCbl insertion or damaged Cbl removal. With the series of structural snapshots now available, we now describe here the molecular basis of G-protein assisted adenosylcobalamin-dependent mutase maturation, explaining how GTP binding prepares a mutase for cofactor delivery and how GTP hydrolysis allows the mutase to capture the cofactor.

Structural insight into G-protein chaperone-mediated maturation of a bacterial adenosylcobalamin-dependent mutase.,Vaccaro FA, Faber DA, Andree GA, Born DA, Kang G, Fonseca DR, Jost M, Drennan CL J Biol Chem. 2023 Jul 28:105109. doi: 10.1016/j.jbc.2023.105109. PMID:37517695^[4]

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

References

↑ Cracan V, Banerjee R. Novel coenzyme B12-dependent interconversion of isovaleryl-CoA and pivalyl-CoA. J Biol Chem. 2012 Feb 3;287(6):3723-32. PMID:22167181 doi:10.1074/jbc.M111.320051
↑ Jost M, Cracan V, Hubbard PA, Banerjee R, Drennan CL. Visualization of a radical B12 enzyme with its G-protein chaperone. Proc Natl Acad Sci U S A. 2015 Feb 24;112(8):2419-24. doi:, 10.1073/pnas.1419582112. Epub 2015 Feb 9. PMID:25675500 doi:http://dx.doi.org/10.1073/pnas.1419582112
↑ Li Z, Kitanishi K, Twahir UT, Cracan V, Chapman D, Warncke K, Banerjee R. Cofactor Editing by the G-protein Metallochaperone Domain Regulates the Radical B(12) Enzyme IcmF. J Biol Chem. 2017 Mar 10;292(10):3977-3987. PMID:28130442 doi:10.1074/jbc.M117.775957
↑ Vaccaro FA, Faber DA, Andree GA, Born DA, Kang G, Fonseca DR, Jost M, Drennan CL. Structural insight into G-protein chaperone-mediated maturation of a bacterial adenosylcobalamin-dependent mutase. J Biol Chem. 2023 Jul 28:105109. PMID:37517695 doi:10.1016/j.jbc.2023.105109

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/8sta"

Categories: Cupriavidus metallidurans CH34 | Large Structures | Drennan CL | Vaccaro FA

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8sta is ON HOLD  until Paper Publication
+==Isobutyryl-CoA mutase fused in the presence of GMPPCP==
+<StructureSection load='8sta' size='340' side='right'caption='[[8sta]], [[Resolution|resolution]] 7.30&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8sta]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Cupriavidus_metallidurans_CH34 Cupriavidus metallidurans CH34]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8STA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8STA 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]] 7.3&#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=8sta FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8sta OCA], [https://pdbe.org/8sta PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8sta RCSB], [https://www.ebi.ac.uk/pdbsum/8sta PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8sta ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/ICMF_CUPMC ICMF_CUPMC] Catalyzes the reversible interconversion of isobutyryl-CoA and n-butyryl-CoA, and to a much lesser extent, of pivalyl-CoA and isovaleryl-CoA, using radical chemistry (PubMed:22167181). Also exhibits GTPase activity, associated with its G-protein domain (MeaI) that functions as a chaperone that assists cofactor delivery and proper holo-enzyme assembly (PubMed:22167181, PubMed:25675500). The G-domain of IcmF has also a role in its cofactor repair (PubMed:28130442). Does not display ATPase activity.<ref>PMID:22167181</ref> <ref>PMID:25675500</ref> <ref>PMID:28130442</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+G-protein metallochaperones are essential for the proper maturation of numerous metalloenzymes. The G-protein chaperone MMAA in humans (MeaB in bacteria) uses GTP hydrolysis to facilitate the delivery of adenosylcobalamin (AdoCbl) to AdoCbl-dependent methylmalonyl-CoA mutase, an essential metabolic enzyme. This G-protein chaperone also facilitates the removal of damaged cobalamin (Cbl) for repair. Although most chaperones are standalone proteins, IcmF (isobutyryl-CoA mutase fused) has a G-protein domain covalently attached to its target mutase. We previously showed that dimeric MeaB undergoes a 180 degrees rotation to reach a state capable of GTP hydrolysis (an active G-protein state), in which so-called switch III residues of one protomer contact the G-nucleotide of the other protomer. However, it was unclear whether other G-protein chaperones also adopted this conformation. Here we show that the G-protein domain in a fused system forms a similar active conformation, requiring IcmF oligomerization. IcmF oligomerizes both upon Cbl damage and in the presence of the nonhydrolyzable GTP analog, guanosine-5'-[(beta,gamma)-methyleno]triphosphate, forming supramolecular complexes observable by mass photometry and electron microscopy. Cryogenic electron microscopy (cryo-EM) structural analysis reveals that the second protomer of the G-protein intermolecular dimer props open the mutase active site using residues of switch III as a wedge, allowing for AdoCbl insertion or damaged Cbl removal. With the series of structural snapshots now available, we now describe here the molecular basis of G-protein assisted adenosylcobalamin-dependent mutase maturation, explaining how GTP binding prepares a mutase for cofactor delivery and how GTP hydrolysis allows the mutase to capture the cofactor.
-Authors: Vaccaro, F.A., Drennan, C.L.
+Structural insight into G-protein chaperone-mediated maturation of a bacterial adenosylcobalamin-dependent mutase.,Vaccaro FA, Faber DA, Andree GA, Born DA, Kang G, Fonseca DR, Jost M, Drennan CL J Biol Chem. 2023 Jul 28:105109. doi: 10.1016/j.jbc.2023.105109. PMID:37517695<ref>PMID:37517695</ref>
-Description: Isobutyryl-CoA mutase fused in the presence of GMPPCP
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Drennan, C.L]]
+<div class="pdbe-citations 8sta" style="background-color:#fffaf0;"></div>
-[[Category: Vaccaro, F.A]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Cupriavidus metallidurans CH34]]
+[[Category: Large Structures]]
+[[Category: Drennan CL]]
+[[Category: Vaccaro FA]]

8sta

From Proteopedia

Revision as of 05:32, 9 August 2023

Isobutyryl-CoA mutase fused in the presence of GMPPCP

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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