title: Direct evidence for the size and conformational variability of the pyruvate dehydrogenase complex revealed by three-dimensional electron microscopy. The "breathing" core and its functional relationship to protein dynamics.
abstract: Structural studies by three-dimensional electron microscopy of the Saccharomyces cerevisiae truncated dihydrolipoamide acetyltransferase (tE(2)) component of the pyruvate dehydrogenase complex reveal an extraordinary example of protein dynamics. The tE(2) forms a 60-subunit core with the morphology of a pentagonal dodecahedron and consists of 20 cone-shaped trimers interconnected by 30 bridges. Frozen-hydrated and stained molecules of tE(2) in the same field vary in size approximately 20%. Analyses of the data show that the size distribution is bell-shaped, and there is an approximately 40-A difference in the diameter of the smallest and largest structures that corresponds to approximately 14 A of variation in the length of the bridge between interconnected trimers. Companion studies of mature E(2) show that the complex of the intact subunit exhibits a similar size variation. The x-ray structure of Bacillus stearothermophilus tE(2) shows that there is an approximately 10-A gap between adjacent trimers and that the trimers are interconnected by the potentially flexible C-terminal ends of two adjacent subunits. We propose that this springlike feature is involved in a thermally driven expansion and contraction of the core and, since it appears to be a common feature in the phylogeny of pyruvate dehydrogenase complexes, protein dynamics is an integral component of the function of these multienzyme complexes.
authors: Department of Pathology and Laboratory Medicine, University of Texas, Houston Medical School, Houston, Texas 77030, USA.
authors: Z H
authors: ZH
authors: Zhou
authors: W
authors: W
authors: Liao
authors: R H
authors: RH
authors: Cheng
authors: J E
authors: JE
authors: Lawson
authors: D B
authors: DB
authors: McCarthy
authors: L J
authors: LJ
authors: Reed
authors: J K
authors: JK
authors: Stoops
mesh_terms: D000123:Acetyltransferases / Q000737:chemistry* / Q000648:ultrastructure*; D001665:Binding Sites; D051047:Dihydrolipoyllysine-Residue Acetyltransferase; D001411:Geobacillus stearothermophilus / Q000201:enzymology; D007091:Image Processing, Computer-Assisted; D008854:Microscopy, Electron; D008958:Models, Molecular; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D021122:Protein Subunits; D011768:Pyruvate Dehydrogenase Complex / Q000737:chemistry* / Q000648:ultrastructure*; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D029701:Saccharomyces cerevisiae Proteins
chemical_list: D021122:Protein Subunits; D011768:Pyruvate Dehydrogenase Complex; D029701:Saccharomyces cerevisiae Proteins; D000123:Acetyltransferases; D051047:Dihydrolipoyllysine-Residue Acetyltransferase; C494879:LAT1 protein, S cerevisiae