Principles of quasi-equivalence and Euclidean geometry govern the assembly of cubic and dodecahedral cores of pyruvate dehydrogenase complexes

Principles of quasi-equivalence and Euclidean geometry govern the assembly of cubic and dodecahedral cores of pyruvate dehydrogenase complexes

^*Departments of Biological Structure and Biochemistry, Biomolecular Structure Center, and Howard Hughes Medical Institute, University of Washington, Box 357742, Seattle, WA 98195-7742; ^‡Cambridge Centre for Molecular Recognition, Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, United Kingdom; and ^§Department of Biochemistry, Agricultural University, Dreyenlaan 3, 6703 HA Wageningen, The Netherlands

Communicated by Vincent Massey, University of Michigan Medical School, Ann Arbor, MI (received for review September 8, 1998)

Abstract

The pyruvate dehydrogenase multienzyme complex (M _r of 5–10 million) is assembled around a structural core formed of multiple copies of dihydrolipoyl acetyltransferase (E2p), which exhibits the shape of either a cube or a dodecahedron, depending on the source. The crystal structures of the 60-meric dihydrolipoyl acyltransferase cores of Bacillus stearothermophilus and Enterococcus faecalis pyruvate dehydrogenase complexes were determined and revealed a remarkably hollow dodecahedron with an outer diameter of ≈237 Å, 12 large openings of ≈52 Å diameter across the fivefold axes, and an inner cavity with a diameter of ≈118 Å. Comparison of cubic and dodecahedral E2p assemblies shows that combining the principles of quasi-equivalence formulated by Caspar and Klug [Caspar, D. L. & Klug, A. (1962) Cold Spring Harbor Symp. Quant. Biol. 27, 1–4] with strict Euclidean geometric considerations results in predictions of the major features of the E2p dodecahedron matching the observed features almost exactly.

Footnotes

↵ † Present address: Department of Biochemistry, University of Leicester, University Road, Leicester LE1 7RH, United Kingdom.
↵ ¶ To whom reprint requests should be addressed at: Biomolecular Structure Center, University of Washington, Health Sciences Center, K-428, Box 357742, Seattle, WA 98195-7422. e-mail: bmsc{at}gouda.bmsc.washington.edu.
Data deposition: The atomic coordinates have been deposited in the Protein Data Bank, Biology Department, Brookhaven National Laboratory, Upton, NY 11973 (PDB ID code 1B5S).
ABBREVIATIONS:

E2,

dihydrolipoyl acyltransferase;

E2p,

dihydrolipoyl acetyltransferase;

PDH,

pyruvate dehydrogenase