A new level of architectural complexity in the human pyruvate dehydrogenase complex

Smolle, M., Prior, A.E., Brown, A.E., Cooper, A., Byron, O. and Lindsay, J.G. (2006) A new level of architectural complexity in the human pyruvate dehydrogenase complex. Journal of Biological Chemistry, 281(28), pp. 19772-19780. (doi:10.1074/jbc.M601140200)

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Publisher's URL: http://www.jbc.org/

Abstract

Mammalian pyruvate dehydrogenase multienzyme complex (PDC) is a key metabolic assembly comprising a 60-meric pentagonal dodecahedral E2 (dihydrolipoamide acetyltransferase) core attached to which are 30 pyruvate decarboxylase E1 heterotetramers and 6 dihydrolipoamide dehydrogenase E3 homodimers at maximal occupancy. Stable E3 integration is mediated by an accessory E3-binding protein (E3BP) located on each of the 12 E2 icosahedral faces. Here, we present evidence for a novel subunit organization in which E3 and E3BP form subcomplexes with a 1:2 stoichiometry implying the existence of a network of E3 “cross-bridges” linking pairs of E3BPs across the surface of the E2 core assembly. We have also determined a low resolution structure for a truncated E3BP/E3 subcomplex using small angle x-ray scattering showing one of the E3BP lipoyl domains docked into the E3 active site. This new level of architectural complexity in mammalian PDC contrasts with the recently published crystal structure of human E3 complexed with its cognate subunit binding domain and provides important new insights into subunit organization, its catalytic mechanism and regulation by the intrinsic PDC kinase.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Cooper, Professor Alan and Byron, Professor Olwyn
Authors: Smolle, M., Prior, A.E., Brown, A.E., Cooper, A., Byron, O., and Lindsay, J.G.
College/School:College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:Journal of Biological Chemistry
Journal Abbr.:J Biol Chem.
Publisher:American Society for Biochemistry and Molecular Biology, Inc.
ISSN:0021-9258
ISSN (Online):1083-351X

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