title: The remarkable structural and functional organization of the eukaryotic pyruvate dehydrogenase complexes.
abstract: The three-dimensional reconstruction of the bovine kidney pyruvate dehydrogenase complex (M(r) approximately 7.8 x 10(6)) comprising about 22 molecules of pyruvate dehydrogenase (E(1)) and about 6 molecules of dihydrolipoamide dehydrogenase (E(3)) with its binding protein associated with the 60-subunit dihydrolipoamide acetyltransferase (E(2)) core provides considerable insight into the structural and functional organization of the largest multienzyme complex known. The structure shows that potentially 60 centers for acetyl-CoA synthesis are organized in sets of three at each of the 20 vertices of the pentagonal dodecahedral core. These centers consist of three E(1) molecules bound to one E(2) trimer adjacent to an E(3) molecule in each of 12 pentagonal openings. The E(1) components are anchored to the E(1)-binding domain of the E(2) subunits through an approximately 50-A-long linker. Three of these linkers emanate from the outside edges of the triangular base of the E(2) trimer and form a cage around its base that may shelter the lipoyl domains and the E(1) and E(2) active sites. The docking of the atomic structures of E(1) and the E(1) binding and lipoyl domains of E(2) in the electron microscopy map gives a good fit and indicates that the E(1) active site is approximately 95 A above the base of the trimer. We propose that the lipoyl domains and its tether (swinging arm) rotate about the E(1)-binding domain of E(2,) which is centrally located 45-50 A from the E(1), E(2), and E(3) active sites, and that the highly flexible breathing core augments the transfer of intermediates between active sites.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Texas Medical School, Houston, TX 77030, USA.
authors.forename: Z H
authors.initials: ZH
authors.lastname: Zhou
authors.forename: D B
authors.initials: DB
authors.lastname: McCarthy
authors.forename: C M
authors.initials: CM
authors.lastname: O'Connor
authors.forename: L J
authors.initials: LJ
authors.lastname: Reed
authors.forename: J K
authors.initials: JK
authors.lastname: Stoops
mesh_terms: D000818:Animals; D002417:Cattle; D020285:Cryoelectron Microscopy; D007668:Kidney / Q000201:enzymology; D008958:Models, Molecular; D011487:Protein Conformation; D011768:Pyruvate Dehydrogenase Complex / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D011768:Pyruvate Dehydrogenase Complex