The catalytic core of an archaeal 2-oxoacid dehydrogenase multienzyme complex is a 42-mer protein assembly

N L Marrott, J J T Marshall, D I Svergun, Susan J Crennell, David W Hough, Michael J Danson, Johannes M H van den Elsen

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14 Citations (SciVal)


The dihydrolipoyl acyl-transferase (E2) enzyme forms the structural and catalytic core of the tripartite 2-oxoacid dehydrogenase multienzyme complexes of the central metabolic pathways. Although this family of multienzyme complexes shares a common architecture, their E2 cores form homo-trimers that, depending on the source, further associate into either octahedral (24-mer) or icosahedral (60-mer) assemblies, as predicted by the principles of quasi-equivalence. In the crystal structure of the E2 core from Thermoplasmaacidophilum, a thermophilic archaeon, the homo-trimers assemble into a unique 42-mer oblate spheroid. Analytical equilibrium centrifugation and small-angle X-ray scattering analyses confirm that this catalytically active 1.08MDa assembly exists as a single species in solution, forming a hollow spheroid with a maximum diameter of 220Å. In this paper we show that a monodisperse macromolecular assembly, built from identical subunits in non-identical environments, forms an irregular protein shell via non-equivalent interactions. This unusually irregular protein shell, combining cubic and dodecahedral geometrical elements, expands on the concept of quasi-equivalence as a basis for understanding macromolecular assemblies by showing that cubic point group symmetry is not a physical requirement in multienzyme assembly. These results extend our basic knowledge of protein assembly and greatly expand the number of possibilities to manipulate self-assembling biological complexes to be utilized in innovative nanotechnology applications.
Original languageEnglish
Pages (from-to)713-723
Number of pages11
JournalFEBS Journal
Issue number5
Early online date19 Jan 2012
Publication statusPublished - Mar 2012


  • X-ray crystallography
  • multienzyme complex
  • archaea
  • thermophile
  • macromolecular assembly


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