7q5r

From Proteopedia

(Difference between revisions)

Current revision

Protein community member pyruvate dehydrogenase complex E2 core from C. thermophilum

Structural highlights

7q5r is a 60 chain structure with sequence from Chaetomium thermophilum var. thermophilum DSM 1495. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.84Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ODP2_CHATD The 10-megadalton pyruvate dehydrogenase complex contains multiple copies of three enzymatic components: pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2) and lipoamide dehydrogenase (E3) and catalyzes the overall oxidative decarboxylation of pyruvate to form acetyl-CoA and CO(2) (PubMed:33567276, PubMed:34836937, PubMed:35093201). Within the complex, pyruvate and thiamine pyrophosphate (TPP or vitamin B1) are bound by pyruvate dehydrogenase E1 subunits alpha and beta and pyruvate is decarboxylated leading to the 2-carbon hydrohyethyl bound to TPP. The E2 component contains covalently-bound lipoyl cofactors and transfers the hydroxyethyl group from TPP to an oxidized form of covalently bound lipoamide, and the resulting acetyl group is then transferred to free coenzyme A to form acetyl-CoA and reduced dihydrolipoamide-E2. Finally, the flavoprotein dihydrolipoamide dehydrogenase (E3) re-oxidizes the lipoyl group of dihydrolipoamide-E2 to form lipoamide-E2 and NADH. A fourth subunit, E3BP, is responsible for tethering E3 in proximity to the core, forming the entire metabolon (Probable).^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

Cellular function is underlined by megadalton assemblies organizing in proximity, forming communities. Metabolons are protein communities involving metabolic pathways such as protein, fatty acid, and thioesters of coenzyme-A synthesis. Metabolons are highly heterogeneous due to their function, making their analysis particularly challenging. Here, we simultaneously characterize metabolon-embedded architectures of a 60S pre-ribosome, fatty acid synthase, and pyruvate/oxoglutarate dehydrogenase complex E2 cores de novo. Cryo-electron microscopy (cryo-EM) 3D reconstructions are resolved at 3.84-4.52 A resolution by collecting <3,000 micrographs of a single cellular fraction. After combining cryo-EM with artificial intelligence-based atomic modeling and de novo sequence identification methods, at this resolution range, polypeptide hydrogen bonding patterns are discernible. Residing molecular components resemble their purified counterparts from other eukaryotes but also exhibit substantial conformational variation with potential functional implications. Our results propose an integrated tool, boosted by machine learning, that opens doors for structural systems biology spearheaded by cryo-EM characterization of native cell extracts.

Cryo-EM and artificial intelligence visualize endogenous protein community members.,Skalidis I, Kyrilis FL, Tuting C, Hamdi F, Chojnowski G, Kastritis PL Structure. 2022 Jan 19. pii: S0969-2126(22)00001-6. doi:, 10.1016/j.str.2022.01.001. PMID:35093201^[5]

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

References

↑ Kyrilis FL, Semchonok DA, Skalidis I, Tüting C, Hamdi F, O'Reilly FJ, Rappsilber J, Kastritis PL. Integrative structure of a 10-megadalton eukaryotic pyruvate dehydrogenase complex from native cell extracts. Cell Rep. 2021 Feb 9;34(6):108727. PMID:33567276 doi:10.1016/j.celrep.2021.108727
↑ Tuting C, Kyrilis FL, Muller J, Sorokina M, Skalidis I, Hamdi F, Sadian Y, Kastritis PL. Cryo-EM snapshots of a native lysate provide structural insights into a metabolon-embedded transacetylase reaction. Nat Commun. 2021 Nov 26;12(1):6933. doi: 10.1038/s41467-021-27287-4. PMID:34836937 doi:http://dx.doi.org/10.1038/s41467-021-27287-4
↑ Skalidis I, Kyrilis FL, Tuting C, Hamdi F, Chojnowski G, Kastritis PL. Cryo-EM and artificial intelligence visualize endogenous protein community members. Structure. 2022 Jan 19. pii: S0969-2126(22)00001-6. doi:, 10.1016/j.str.2022.01.001. PMID:35093201 doi:http://dx.doi.org/10.1016/j.str.2022.01.001
↑ Kyrilis FL, Semchonok DA, Skalidis I, Tüting C, Hamdi F, O'Reilly FJ, Rappsilber J, Kastritis PL. Integrative structure of a 10-megadalton eukaryotic pyruvate dehydrogenase complex from native cell extracts. Cell Rep. 2021 Feb 9;34(6):108727. PMID:33567276 doi:10.1016/j.celrep.2021.108727
↑ Skalidis I, Kyrilis FL, Tuting C, Hamdi F, Chojnowski G, Kastritis PL. Cryo-EM and artificial intelligence visualize endogenous protein community members. Structure. 2022 Jan 19. pii: S0969-2126(22)00001-6. doi:, 10.1016/j.str.2022.01.001. PMID:35093201 doi:http://dx.doi.org/10.1016/j.str.2022.01.001

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/7q5r"

@@ Line 3: / Line 3: @@
 <StructureSection load='7q5r' size='340' side='right'caption='[[7q5r]], [[Resolution|resolution]] 3.84&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[7q5r]] is a 60 chain structure with sequence from [https://en.wikipedia.org/wiki/Chaetomium_thermophilum_(strain_dsm_1495_/_cbs_144.50_/_imi_039719) Chaetomium thermophilum (strain dsm 1495 / cbs 144.50 / imi 039719)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7Q5R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Q5R FirstGlance]. <br>
+<table><tr><td colspan='2'>[[7q5r]] is a 60 chain structure with sequence from [https://en.wikipedia.org/wiki/Chaetomium_thermophilum_var._thermophilum_DSM_1495 Chaetomium thermophilum var. thermophilum DSM 1495]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7Q5R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Q5R FirstGlance]. <br>
-</td></tr><tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Dihydrolipoyllysine-residue_acetyltransferase Dihydrolipoyllysine-residue acetyltransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.12 2.3.1.12] </span></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]] 3.84&#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=7q5r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7q5r OCA], [https://pdbe.org/7q5r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7q5r RCSB], [https://www.ebi.ac.uk/pdbsum/7q5r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7q5r ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/G0S4X6_CHATD G0S4X6_CHATD]] The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2).[RuleBase:RU361137]
+[https://www.uniprot.org/uniprot/ODP2_CHATD ODP2_CHATD] The 10-megadalton pyruvate dehydrogenase complex contains multiple copies of three enzymatic components: pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2) and lipoamide dehydrogenase (E3) and catalyzes the overall oxidative decarboxylation of pyruvate to form acetyl-CoA and CO(2) (PubMed:33567276, PubMed:34836937, PubMed:35093201). Within the complex, pyruvate and thiamine pyrophosphate (TPP or vitamin B1) are bound by pyruvate dehydrogenase E1 subunits alpha and beta and pyruvate is decarboxylated leading to the 2-carbon hydrohyethyl bound to TPP. The E2 component contains covalently-bound lipoyl cofactors and transfers the hydroxyethyl group from TPP to an oxidized form of covalently bound lipoamide, and the resulting acetyl group is then transferred to free coenzyme A to form acetyl-CoA and reduced dihydrolipoamide-E2. Finally, the flavoprotein dihydrolipoamide dehydrogenase (E3) re-oxidizes the lipoyl group of dihydrolipoamide-E2 to form lipoamide-E2 and NADH. A fourth subunit, E3BP, is responsible for tethering E3 in proximity to the core, forming the entire metabolon (Probable).<ref>PMID:33567276</ref> <ref>PMID:34836937</ref> <ref>PMID:35093201</ref> <ref>PMID:33567276</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 18: / Line 18: @@
 </div>
 <div class="pdbe-citations 7q5r" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Pyruvate dehydrogenase 3D structures|Pyruvate dehydrogenase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Dihydrolipoyllysine-residue acetyltransferase]]
+[[Category: Chaetomium thermophilum var. thermophilum DSM 1495]]
 [[Category: Large Structures]]
-[[Category: Chojnowski, G]]
+[[Category: Chojnowski G]]
-[[Category: Hamdi, F]]
+[[Category: Hamdi F]]
-[[Category: Kastritis, P L]]
+[[Category: Kastritis PL]]
-[[Category: Kyrilis, F L]]
+[[Category: Kyrilis FL]]
-[[Category: Skalidis, I]]
+[[Category: Skalidis I]]
-[[Category: Tueting, C]]
+[[Category: Tueting C]]
-[[Category: Dihydrolipoyl]]
-[[Category: E2]]
-[[Category: Pyruvate]]
-[[Category: Transacetylase]]
-[[Category: Transferase]]

7q5r

From Proteopedia

Current revision

Protein community member pyruvate dehydrogenase complex E2 core from C. thermophilum

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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