title: The catalytic core of an archaeal 2-oxoacid dehydrogenase multienzyme complex is a 42-mer protein assembly.
abstract: 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 Thermoplasma acidophilum, 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 1.08 MDa assembly exists as a single species in solution, forming a hollow spheroid with a maximum diameter of 220 Å. 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.
authors.affiliation: Department of Biology and Biochemistry, Centre for Extremophile Research, University of Bath, UK.
authors.forename: Nia L
authors.initials: NL
authors.lastname: Marrott
authors.forename: Jacqueline J T
authors.initials: JJ
authors.lastname: Marshall
authors.forename: Dmitri I
authors.initials: DI
authors.lastname: Svergun
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Crennell
authors.forename: David W
authors.initials: DW
authors.lastname: Hough
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Danson
authors.forename: Jean M H
authors.initials: JM
authors.lastname: van den Elsen
mesh_terms: D019843:Archaeal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D009097:Multienzyme Complexes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation; D013822:Thermoplasma / Q000201:enzymology*
chemical_list: D019843:Archaeal Proteins; D009097:Multienzyme Complexes