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X-Ray Crystallography to Study the Oligomeric State Transition of the Thermotoga maritima M42 Aminopeptidase TmPep1050
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Solution structure and characterisation of the human pyruvate dehydrogenase complex core assembly
S Vijayakrishnan1, S M Kelly, R J C Gilbert
1Division of Molecular and Cell Biology, Faculty of Biomedical and Life Sciences, Davidson Building, University of Glasgow, Glasgow G12 8QQ, UK.
Journal of Molecular Biology
|April 6, 2010
Summary
The mammalian pyruvate dehydrogenase complex (PDC) core structure favors the
Area of Science:
- Biochemistry
- Structural Biology
- Molecular Biology
Background:
- The mammalian pyruvate dehydrogenase complex (PDC) is crucial for glucose homeostasis and energy metabolism.
- Two models, 'addition' and 'substitution', exist for the organization of the PDC core (E2+E3BP subunits).
Purpose of the Study:
- To determine the low-resolution structures of human recombinant and native bovine PDC cores.
- To resolve the conflicting models of PDC core organization.
Main Methods:
- Small-angle X-ray scattering (SAXS) and small-angle neutron scattering (SANS).
- Negative-stain and cryo-electron microscopy (cryo-EM).
- Analytical ultracentrifugation, circular dichroism, and fluorescence spectroscopy.
Main Results:
- SAXS and SANS data revealed open pentagonal core faces, supporting the 'substitution' model.
- Cryo-EM confirmed open pentagonal faces and showed increased order with E3 binding.
- Analytical ultracentrifugation and stability studies further corroborated the substitution model and highlighted E3BP's role in core destabilization.
Conclusions:
- The study provides strong evidence for the 'substitution' model of mammalian PDC core organization.
- The structural features and stability of the mammalian PDC core are adapted for fine-tuned metabolic regulation.
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