On the unique structural organization of the Saccharomyces cerevisiae pyruvate dehydrogenase complex

Dihydrolipoamide acyltransferase (E(2)), and structural component of the three classes of multienzyme complexes that catalyze the oxidative decarboxylation of alpha-keto acids, forms the central core to which the other components attach, We have determined the structures of the truncated 60-mer core dihydrolipoamide acetyltransferase (tE(2)) of the Saccharomyces cerevisiae pyruvate dehydrogenase complex and complexes of the tE(2) core associated with a truncated binding protein (tBP), intact binding protein (BP), and the BP associated with its dihydrolipoamide dehydrogenase (BP . E(3)). The tE(2) core is a pentagonal dodecahedron consisting of 20 cone-shaped trimers interconnected by 30 bridges, Previous studies have given rise to the generally accepted belief that the other components are bound on the outside of the E(2) scaffold, However, this investigation shows that the 12 large openings in the tE(2) core permit the entrance of tBP, BP, and BP . E(3) into a large central cavity where the BP component apparently binds near the tip of the tE(2) trimer, The bone-shaped E(3) molecule is anchored inside the central cavity through its interaction with BP, One end of E(3) as its catalytic site within the surface of the scaffold for interaction with other external catalytic domains, Though tE(2) has 60 potential binding sites, it binds only about 30 copies of tBP, 15 of BP, and 12 of BP . E(3). Thus, E(2) is unusual in that the stoichiometry and arrangement of the tBP, BP, and E(3) . BP components are determined by the geometric constraints of the underlying scaffold.