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 language | English (US) |
|---|---|
| Pages (from-to) | 5757-5764 |
| Number of pages | 8 |
| Journal | Journal of Biological Chemistry |
| Volume | 272 |
| Issue number | 9 |
| DOIs | |
| State | Published - Feb 28 1997 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry
Cite this
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 journal › Article
}
TY - JOUR
T1 - On the unique structural organization of the Saccharomyces cerevisiae pyruvate dehydrogenase complex
AU - Stoops, James K.
AU - Cheng, R. Holland
AU - Yazdi, Mohammed A.
AU - Maeng, Cheol Young
AU - Schroeter, John P.
AU - Klueppelberg, Uwe
AU - Kolodziej, Steven J.
AU - Baker, Timothy S.
AU - Reed, Lester J.
PY - 1997/2/28
Y1 - 1997/2/28
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0031041382&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031041382&partnerID=8YFLogxK
U2 - 10.1074/jbc.272.9.5757
DO - 10.1074/jbc.272.9.5757
M3 - Article
C2 - 9038189
AN - SCOPUS:0031041382
VL - 272
SP - 5757
EP - 5764
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 9
ER -