Journal Article

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

Forsberg, B. O., Howard, R. J., Lindahl, E., Aibara, S., Mortezaei, N.

2020

Overview

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. The pyruvate dehydrogenase complex (PDC) is a multienzyme complex connecting glycolysis to mitochondrial oxidation of pyruvate. Cryo-EM analysis of PDC from Neurospora crassa reveals localization of fungi-specific protein X (PX) and confirms that it functions like the mammalian E3BP, recruiting the E3 component of PDC.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 147/143 / 147/28 / 631/45/612/1240 / 631/535/1258/1259 / 631/57/1464 / 639/705/531 / Aerobic respiration / binding protein / binding site / Binding Sites / carboxy terminal sequence / chemistry / Cryoelectron Microscopy / Dehydrogenase / Dehydrogenases / Divergence / E3 binding protein / Electron microscopy / Electron transport / enzyme activity / filamentous fungus / fungal protein / Fungal Proteins / Fungal Proteins - chemistry / Fungal Proteins - metabolism / Fungi / fungus / genetics / Glycolysis / Humanities and Social Sciences / Localization / Mammalia / Mammals / metabolism / Mitochondria / Models, Molecular / Molecular / molecular model / multidisciplinary / Neurospora / Neurospora crassa / Neurospora crassa - chemistry / nonhuman / Occlusion / Oxidation / protein binding / Protein Conformation / protein domain / Protein Domains / protein motif / protein structure / Protein X / Proteins / Pyruvate dehydrogenase (lipoamide) / pyruvate dehydrogenase complex / Pyruvate Dehydrogenase Complex - chemistry / Pyruvate Dehydrogenase Complex - genetics / Pyruvate Dehydrogenase Complex - metabolism / Pyruvic acid / Saccharomyces cerevisiae / Science / Science (multidisciplinary) / Symmetry / ultrastructure / unclassified drug