8PIU
60-meric complex of dihydrolipoamide acetyltransferase (E2) of the human pyruvate dehydrogenase complex
This is a non-PDB format compatible entry.
Summary for 8PIU
| Entry DOI | 10.2210/pdb8piu/pdb |
| EMDB information | 17691 17694 18616 18617 |
| Descriptor | Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial (1 entity in total) |
| Functional Keywords | pyruvate dehydrogenase complex, pdhc, e2, cryo-em, transferase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 60 |
| Total formula weight | 3588709.92 |
| Authors | Zdanowicz, R.,Afanasyev, P.,Boehringer, D.,Glockshuber, R. (deposition date: 2023-06-22, release date: 2024-07-10, Last modification date: 2024-07-31) |
| Primary citation | Zdanowicz, R.,Afanasyev, P.,Pruska, A.,Harrison, J.A.,Giese, C.,Boehringer, D.,Leitner, A.,Zenobi, R.,Glockshuber, R. Stoichiometry and architecture of the human pyruvate dehydrogenase complex. Sci Adv, 10:eadn4582-eadn4582, 2024 Cited by PubMed Abstract: The pyruvate dehydrogenase complex (PDHc) is a key megaenzyme linking glycolysis with the citric acid cycle. In mammalian PDHc, dihydrolipoamide acetyltransferase (E2) and the dihydrolipoamide dehydrogenase-binding protein (E3BP) form a 60-subunit core that associates with the peripheral subunits pyruvate dehydrogenase (E1) and dihydrolipoamide dehydrogenase (E3). The structure and stoichiometry of the fully assembled, mammalian PDHc or its core remained elusive. Here, we demonstrate that the human PDHc core is formed by 48 E2 copies that bind 48 E1 heterotetramers and 12 E3BP copies that bind 12 E3 homodimers. Cryo-electron microscopy, together with native and cross-linking mass spectrometry, confirmed a core model in which 8 E2 homotrimers and 12 E2-E2-E3BP heterotrimers assemble into a pseudoicosahedral particle such that the 12 E3BP molecules form six E3BP-E3BP intertrimer interfaces distributed tetrahedrally within the 60-subunit core. The even distribution of E3 subunits in the peripheral shell of PDHc guarantees maximum enzymatic activity of the megaenzyme. PubMed: 39018392DOI: 10.1126/sciadv.adn4582 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.9 Å) |
Structure validation
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