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

Z. Hong Zhou, Wangcai Liao, R. Holland Cheng, J. E. Lawson, D. B. McCarthy, Lester J. Reed, James K. Stoops

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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 tE2 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 tE2 in the same field vary in size ∼20%. Analyses of the data show that the size distribution is bell-shaped, and there is an approximately 40-Å difference in the diameter of the smallest and largest structures that corresponds to ∼14 Å of variation in the length of the bridge between interconnected trimers. Companion studies of mature E2 show that the complex of the intact subunit exhibits a similar size variation. The x-ray structure of Bacillus stearothermophilus tE2 shows that there is an ∼10-Å 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.

Original languageEnglish (US)
Pages (from-to)21704-21713
Number of pages10
JournalJournal of Biological Chemistry
Volume276
Issue number24
DOIs
StatePublished - Jun 15 2001
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry

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