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TitleArrangement and symmetry of the fungal E3BP-containing core of the pyruvate dehydrogenase complex.
Journal, issue, pagesNat Commun, Vol. 11, Issue 1, Page 4667, Year 2020
Publish dateSep 16, 2020
AuthorsB O Forsberg / S Aibara / R J Howard / N Mortezaei / E Lindahl /
PubMed AbstractThe 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) ...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.
External linksNat Commun / PubMed:32938938 / PubMed Central
MethodsEM (single particle)
Resolution2.9 - 4.4 Å
Structure data

EMDB-11266:
E2 core of the fungal Pyruvate dehydrogenase complex with flexible/oversym. periphery, structured core and oversym. interior
Method: EM (single particle) / Resolution: 4.1 Å

EMDB-11267:
E2 core of the fungal Pyruvate dehydrogenase complex with flexible/oversym. periphery, structured core and S4X-structured interior.
Method: EM (single particle) / Resolution: 4.4 Å

11268

6zlm

EMDB-11268: E2 core of the fungal Pyruvate dehydrogenase complex with flexible/oversym. periphery, structured core and S4Y-structured interior.
PDB-6zlm: Dihydrolipoyllysine-residue acetyltransferase component of fungal pyruvate dehydrogenase complex with protein X bound
Method: EM (single particle) / Resolution: 4.3 Å

EMDB-11269:
E2 core of the fungal Pyruvate dehydrogenase complex with absent periphery, structured core and empty interior.
Method: EM (single particle) / Resolution: 4.4 Å

11270

6zlo

EMDB-11270, PDB-6zlo:
E2 core of the fungal Pyruvate dehydrogenase complex with asymmetric interior PX30 component
Method: EM (single particle) / Resolution: 2.9 Å

EMDB-11271:
E2 core of the fungal Pyruvate dehydrogenase complex with asymmetric interior PX261 component
Method: EM (single particle) / Resolution: 3.1 Å

Source
  • Neurospora crassa (fungus)
  • neurospora crassa (strain atcc 24698 / 74-or23-1a / cbs 708.71 / dsm 1257 / fgsc 987) (fungus)
KeywordsTRANSFERASE / acetyl transferase / pyruvate dehydrogenase / protein complex / mitochondria / metabolism / tetrahedral icosahedral

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