Cryo-EM Analysis Reveals New Insights into the Mechanism of Action of Pyruvate Carboxylase

Gorka Lasso, Linda P.C. Yu, David Gil, Song Xiang, Liang Tong, Mikel Valle

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Pyruvate carboxylase (PC) is a conserved multifunctional enzyme linked to important metabolic diseases. PC homotetramer is arranged in two layers with two opposing monomers per layer. Cryo-EM explores the conformational variability of PC in the presence of different substrates. The results demonstrate that the biotin-carboxyl carrier protein (BCCP) domain localizes near the biotin carboxylase (BC) domain of its own monomer and travels to the carboxyltransferase (CT) domain of the opposite monomer. All density maps show noticeable conformational differences between layers, mainly for the BCCP and BC domains. This asymmetry may be indicative of a coordination mechanism where monomers from different layers catalyze the BC and CT reactions consecutively. A conformational change of the PC tetramerization (PT) domain suggests a new functional role in communication. A long-range communication pathway between subunits in different layers, via interacting PT-PT and BC-BC domains, may be responsible for the cooperativity of PC from Staphylococcus aureus.

Original languageEnglish (US)
Pages (from-to)1300-1310
Number of pages11
JournalStructure
Volume18
Issue number10
DOIs
StatePublished - Oct 13 2010
Externally publishedYes

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biotin carboxylase
Pyruvate Carboxylase
Carboxyl and Carbamoyl Transferases
Multifunctional Enzymes
Metabolic Diseases
Staphylococcus aureus

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Cryo-EM Analysis Reveals New Insights into the Mechanism of Action of Pyruvate Carboxylase. / Lasso, Gorka; Yu, Linda P.C.; Gil, David; Xiang, Song; Tong, Liang; Valle, Mikel.

In: Structure, Vol. 18, No. 10, 13.10.2010, p. 1300-1310.

Research output: Contribution to journalArticle

Lasso, Gorka ; Yu, Linda P.C. ; Gil, David ; Xiang, Song ; Tong, Liang ; Valle, Mikel. / Cryo-EM Analysis Reveals New Insights into the Mechanism of Action of Pyruvate Carboxylase. In: Structure. 2010 ; Vol. 18, No. 10. pp. 1300-1310.
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