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

James K. Stoops, R. Holland Cheng, Mohammed A. Yazdi, Cheol Young Maeng, John P. Schroeter, Uwe Klueppelberg, Steven J. Kolodziej, Timothy S. Baker, Lester J. Reed

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Dihydrolipoamide acyltransferase (E2), a catalytic and structural component of the three functional classes of multienzyme complexes that catalyze the oxidative decarboxylation of α-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 (tE2) of the Saccharomyces cerevisiae pyruvate dehydrogenase complex and complexes of the tE2 core associated with a truncated binding protein (tBP), intact binding protein (BP), and the BP associated with its dihydrolipoamide dehydrogenase (BP·E3). The tE2 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 E2 scaffold. However, this investigation shows that the 12 large openings in the tE2 core permit the entrance of tBP, BP, and BP·E3 into a large central cavity where the BP component apparently binds near the tip of the tE2 trimer. The bone-shaped E3 molecule is anchored inside the central cavity through its interaction with BP. One end of E3 has its catalytic site within the surface of the scaffold for interaction with other external catalytic domains. Though tE2 has 60 potential binding sites, it binds only about 30 copies of tBP, 15 of BP, and 12 of BP·E3. Thus, E2 is unusual in that the stoichiometry and arrangement of the tBP, BP, and E3-BP components are determined by the geometric constraints of the underlying scaffold.

Original languageEnglish (US)
Pages (from-to)5757-5764
Number of pages8
JournalJournal of Biological Chemistry
Volume272
Issue number9
DOIs
StatePublished - Feb 28 1997
Externally publishedYes

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Pyruvate Dehydrogenase Complex
Yeast
Saccharomyces cerevisiae
Carrier Proteins
Protein Binding
Scaffolds
Catalytic Domain
Dihydrolipoyllysine-Residue Acetyltransferase
Multienzyme Complexes
Dihydrolipoamide Dehydrogenase
Keto Acids
Decarboxylation
Stoichiometry
Cones

ASJC Scopus subject areas

  • Biochemistry

Cite this

Stoops, J. K., Cheng, R. H., Yazdi, M. A., Maeng, C. Y., Schroeter, J. P., Klueppelberg, U., ... Reed, L. J. (1997). On the unique structural organization of the Saccharomyces cerevisiae pyruvate dehydrogenase complex. Journal of Biological Chemistry, 272(9), 5757-5764. https://doi.org/10.1074/jbc.272.9.5757

On the unique structural organization of the Saccharomyces cerevisiae pyruvate dehydrogenase complex. / Stoops, James K.; Cheng, R. Holland; Yazdi, Mohammed A.; Maeng, Cheol Young; Schroeter, John P.; Klueppelberg, Uwe; Kolodziej, Steven J.; Baker, Timothy S.; Reed, Lester J.

In: Journal of Biological Chemistry, Vol. 272, No. 9, 28.02.1997, p. 5757-5764.

Research output: Contribution to journalArticle

Stoops, JK, Cheng, RH, Yazdi, MA, Maeng, CY, Schroeter, JP, Klueppelberg, U, Kolodziej, SJ, Baker, TS & Reed, LJ 1997, 'On the unique structural organization of the Saccharomyces cerevisiae pyruvate dehydrogenase complex', Journal of Biological Chemistry, vol. 272, no. 9, pp. 5757-5764. https://doi.org/10.1074/jbc.272.9.5757
Stoops, James K. ; Cheng, R. Holland ; Yazdi, Mohammed A. ; Maeng, Cheol Young ; Schroeter, John P. ; Klueppelberg, Uwe ; Kolodziej, Steven J. ; Baker, Timothy S. ; Reed, Lester J. / On the unique structural organization of the Saccharomyces cerevisiae pyruvate dehydrogenase complex. In: Journal of Biological Chemistry. 1997 ; Vol. 272, No. 9. pp. 5757-5764.
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