Arrangement and symmetry of the fungal E3BP-containing core of the pyruvate dehydrogenase complex

Nat Commun. 2020 Sep 16;11(1):4667. doi: 10.1038/s41467-020-18401-z.

Abstract

The pyruvate dehydrogenase complex (PDC) is a multienzyme complex central to aerobic respiration, connecting glycolysis to mitochondrial oxidation of pyruvate. Similar to the E3-binding protein (E3BP) of mammalian PDC, PX selectively recruits E3 to the fungal PDC, but its divergent sequence suggests a distinct structural mechanism. Here, we report reconstructions of PDC from the filamentous fungus Neurospora crassa by cryo-electron microscopy, where we find protein X (PX) interior to the PDC core as opposed to substituting E2 core subunits as in mammals. Steric occlusion limits PX binding, resulting in predominantly tetrahedral symmetry, explaining previous observations in Saccharomyces cerevisiae. The PX-binding site is conserved in (and specific to) fungi, and complements possible C-terminal binding motifs in PX that are absent in mammalian E3BP. Consideration of multiple symmetries thus reveals a differential structural basis for E3BP-like function in fungal PDC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Cryoelectron Microscopy
  • Fungal Proteins / chemistry*
  • Fungal Proteins / metabolism
  • Models, Molecular
  • Neurospora crassa / chemistry*
  • Protein Conformation
  • Protein Domains
  • Pyruvate Dehydrogenase Complex / chemistry*
  • Pyruvate Dehydrogenase Complex / genetics
  • Pyruvate Dehydrogenase Complex / metabolism

Substances

  • Fungal Proteins
  • Pyruvate Dehydrogenase Complex