Sectioned schematic view of an icosahedral pyruvate dehydrogenase complex based on electron cryo-microscopic analysis of an E1E2 sub-complex from Bacillus stearothermophilus. Three of the 60 E2 molecules (colored red, green, and yellow) are highlighted. The movement of the swinging E2 lipoyl domain in the annular region between the inner core (cyan) of E2 molecules and the outer shell of 60 E1 molecules (purple) is proposed to be a critical feature underlying active site coupling in the complex. The pyruvate dehydrogenase complex constitutes one of the cornerstones of cellular energy metabolism, mediating the oxidative decarboxylation of pyruvate to generate acetyl CoA, linking glycolysis and the tricarboxylic acid cycle.