Dimerization of a 5-kDa domain defines the architecture of the 5-MDa gammaproteobacterial pyruvate dehydrogenase complex


Loading...

Date

2024-02-09

Publication Type

Journal Article

ETH Bibliography

yes

Citations

Altmetric

Data

Abstract

The Escherichia coli 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 (E23), we show that two of the three PSBDs in the E23 dimerize, that each PSBD dimer cooperatively binds two E1 dimers, and that E3 dimers only bind to the unpaired PSBD in E23. 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.

Publication status

published

Editor

Book title

Volume

10 (6)

Pages / Article No.

Publisher

AAAS

Event

Edition / version

Methods

Software

Geographic location

Date collected

Date created

Subject

Organisational unit

03412 - Glockshuber, Rudolf (emeritus) / Glockshuber, Rudolf (emeritus) check_circle

Notes

Funding

201234 - Structural and functional characterization of filamentous, supramolecular protein complexes in urinary tract infections (SNF)

Related publications and datasets