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Structure paper

TitleDimerization of a 5-kDa domain defines the architecture of the 5-MDa gammaproteobacterial pyruvate dehydrogenase complex.
Journal, issue, pagesSci Adv, Vol. 10, Issue 6, Page eadj6358, Year 2024
Publish dateFeb 9, 2024
AuthorsSarah Meinhold / Rafal Zdanowicz / Christoph Giese / Rudi Glockshuber /
PubMed AbstractThe pyruvate dehydrogenase complex (PDHc) is a ~5 MDa assembly of the catalytic subunits pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2), and dihydrolipoamide dehydrogenase (E3). ...The pyruvate dehydrogenase complex (PDHc) is a ~5 MDa assembly of the catalytic subunits pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2), and dihydrolipoamide dehydrogenase (E3). The PDHc core is a cubic complex of eight E2 homotrimers. Homodimers of the peripheral subunits E1 and E3 associate with the core by binding to the peripheral subunit binding domain (PSBD) of E2. Previous reports indicated that 12 E1 dimers and 6 E3 dimers bind to the 24-meric E2 core. Using an assembly arrested E2 homotrimer (E2), we show that two of the three PSBDs in the E2 dimerize, that each PSBD dimer cooperatively binds two E1 dimers, and that E3 dimers only bind to the unpaired PSBD in E2. This mechanism is preserved in wild-type PDHc, with an E1 dimer:E2 monomer:E3 dimer stoichiometry of 16:24:8. The conserved PSBD dimer interface indicates that PSBD dimerization is the previously unrecognized architectural determinant of gammaproteobacterial PDHc megacomplexes.
External linksSci Adv / PubMed:38324697 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution1.64 - 3.52 Å
Structure data

EMDB-17119, PDB-8orb:
24-meric catalytic domain of dihydrolipoamide acetyltransferase (E2) of the E. coli pyruvate dehydrogenase complex.
Method: EM (single particle) / Resolution: 3.25 Å

EMDB-17126: E. coli pyruvate dehydrogenase (E1) in complex with dihydrolipoamide acetyltransferase (E2) peripheral subunit-binding domain.
Method: EM (single particle) / Resolution: 3.52 Å

PDB-8oqj:
Peripheral subunit binding domain of the E. coli Dihydrolipoamide Acetyltransferase (E2) of the pyruvate dehydrogenase complex
Method: X-RAY DIFFRACTION / Resolution: 1.64 Å

PDB-8osy:
Trimeric catalytic domain of the E. coli Dihydrolipoamide Acetyltransferase (E2) of the pyruvate dehydrogenase complex
Method: X-RAY DIFFRACTION / Resolution: 1.89 Å

Chemicals

ChemComp-ZN:
Unknown entry

ChemComp-HOH:
WATER / Water

Source
  • escherichia coli (E. coli)
KeywordsPROTEIN BINDING / Pyruvate dehydrogenase complex / Binding domain / Dimer / PSBD / TRANSFERASE / PDHc / E2 / cryo-EM / Catalytic domain / Trimer

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