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-Structure paper
タイトル | Structural analysis of an endogenous 4-megadalton succinyl-CoA-generating metabolon. |
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ジャーナル・号・ページ | Commun Biol, Vol. 6, Issue 1, Page 552, Year 2023 |
掲載日 | 2023年5月22日 |
著者 | Ioannis Skalidis / Fotis L Kyrilis / Christian Tüting / Farzad Hamdi / Toni K Träger / Jaydeep Belapure / Gerd Hause / Marta Fratini / Francis J O'Reilly / Ingo Heilmann / Juri Rappsilber / Panagiotis L Kastritis / |
PubMed 要旨 | The oxoglutarate dehydrogenase complex (OGDHc) participates in the tricarboxylic acid cycle and, in a multi-step reaction, decarboxylates α-ketoglutarate, transfers succinyl to CoA, and reduces NAD+. ...The oxoglutarate dehydrogenase complex (OGDHc) participates in the tricarboxylic acid cycle and, in a multi-step reaction, decarboxylates α-ketoglutarate, transfers succinyl to CoA, and reduces NAD+. Due to its pivotal role in metabolism, OGDHc enzymatic components have been studied in isolation; however, their interactions within the endogenous OGDHc remain elusive. Here, we discern the organization of a thermophilic, eukaryotic, native OGDHc in its active state. By combining biochemical, biophysical, and bioinformatic methods, we resolve its composition, 3D architecture, and molecular function at 3.35 Å resolution. We further report the high-resolution cryo-EM structure of the OGDHc core (E2o), which displays various structural adaptations. These include hydrogen bonding patterns confining interactions of OGDHc participating enzymes (E1o-E2o-E3), electrostatic tunneling that drives inter-subunit communication, and the presence of a flexible subunit (E3BPo), connecting E2o and E3. This multi-scale analysis of a succinyl-CoA-producing native cell extract provides a blueprint for structure-function studies of complex mixtures of medical and biotechnological value. |
リンク | Commun Biol / PubMed:37217784 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.35 Å |
構造データ | EMDB-16900, PDB-8oiu: |
由来 |
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キーワード | TRANSFERASE (転移酵素) / Dihydrolipoyl Succinyltransferase / E2 / Oxoglutarate / a-Ketoglutarate |