A Soluble Metabolon Synthesizes the Isoprenoid Lipid Ubiquinone.


Journal

Cell chemical biology
ISSN: 2451-9448
Titre abrégé: Cell Chem Biol
Pays: United States
ID NLM: 101676030

Informations de publication

Date de publication:
18 04 2019
Historique:
received: 16 10 2018
revised: 14 11 2018
accepted: 29 11 2018
pubmed: 29 1 2019
medline: 28 1 2020
entrez: 29 1 2019
Statut: ppublish

Résumé

Ubiquinone (UQ) is a polyprenylated lipid that is conserved from bacteria to humans and is crucial to cellular respiration. How the cell orchestrates the efficient synthesis of UQ, which involves the modification of extremely hydrophobic substrates by multiple sequential enzymes, remains an unresolved issue. Here, we demonstrate that seven Ubi proteins form the Ubi complex, a stable metabolon that catalyzes the last six reactions of the UQ biosynthetic pathway in Escherichia coli. The SCP2 domain of UbiJ forms an extended hydrophobic cavity that binds UQ intermediates inside the 1-MDa Ubi complex. We purify the Ubi complex from cytoplasmic extracts and demonstrate that UQ biosynthesis occurs in this fraction, challenging the current thinking of a membrane-associated biosynthetic process. Collectively, our results document a rare case of stable metabolon and highlight how the supramolecular organization of soluble enzymes allows the modification of hydrophobic substrates in a hydrophilic environment.

Identifiants

pubmed: 30686758
pii: S2451-9456(18)30439-2
doi: 10.1016/j.chembiol.2018.12.001
pii:
doi:

Substances chimiques

Carrier Proteins 0
Escherichia coli Proteins 0
Terpenes 0
UbiJ protein, E coli 0
Ubiquinone 1339-63-5

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

482-492.e7

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2018 Elsevier Ltd. All rights reserved.

Auteurs

Mahmoud Hajj Chehade (M)

Univ. Grenoble Alpes, CNRS, Grenoble INP, TIMC-IMAG, 38000 Grenoble, France.

Ludovic Pelosi (L)

Univ. Grenoble Alpes, CNRS, Grenoble INP, TIMC-IMAG, 38000 Grenoble, France.

Cameron David Fyfe (CD)

Laboratoire de Chimie des Processus Biologiques, Collège de France, Université Pierre et Marie Curie, CNRS UMR 8229, PSL Research University, 11 Place Marcelin Berthelot, 75005 Paris, France.

Laurent Loiseau (L)

Aix Marseille Université, CNRS, Laboratoire Chimie Bactérienne, Institut Microbiologie de la Méditerranée, 31 Chemin Joseph Aiguier, Marseille 13009, France.

Bérengère Rascalou (B)

Univ. Grenoble Alpes, CNRS, Grenoble INP, TIMC-IMAG, 38000 Grenoble, France.

Sabine Brugière (S)

Univ. Grenoble Alpes, CEA, Inserm, BIG-BGE, 38000 Grenoble, France.

Katayoun Kazemzadeh (K)

Univ. Grenoble Alpes, CNRS, Grenoble INP, TIMC-IMAG, 38000 Grenoble, France.

Chau-Duy-Tam Vo (CD)

Laboratoire de Chimie des Processus Biologiques, Collège de France, Université Pierre et Marie Curie, CNRS UMR 8229, PSL Research University, 11 Place Marcelin Berthelot, 75005 Paris, France.

Lidia Ciccone (L)

SOLEIL Synchrotron, L'Orme des Merisiers, 91198 Gif-sur-Yvette, France.

Laurent Aussel (L)

Aix Marseille Université, CNRS, Laboratoire Chimie Bactérienne, Institut Microbiologie de la Méditerranée, 31 Chemin Joseph Aiguier, Marseille 13009, France.

Yohann Couté (Y)

Univ. Grenoble Alpes, CEA, Inserm, BIG-BGE, 38000 Grenoble, France.

Marc Fontecave (M)

Laboratoire de Chimie des Processus Biologiques, Collège de France, Université Pierre et Marie Curie, CNRS UMR 8229, PSL Research University, 11 Place Marcelin Berthelot, 75005 Paris, France.

Frédéric Barras (F)

Aix Marseille Université, CNRS, Laboratoire Chimie Bactérienne, Institut Microbiologie de la Méditerranée, 31 Chemin Joseph Aiguier, Marseille 13009, France; SAMe Unit, Department de Microbiologie, Institut Pasteur, 25 Rue du Dr Roux, 75015 Paris, France.

Murielle Lombard (M)

Laboratoire de Chimie des Processus Biologiques, Collège de France, Université Pierre et Marie Curie, CNRS UMR 8229, PSL Research University, 11 Place Marcelin Berthelot, 75005 Paris, France.

Fabien Pierrel (F)

Univ. Grenoble Alpes, CNRS, Grenoble INP, TIMC-IMAG, 38000 Grenoble, France. Electronic address: fabien.pierrel@univ-grenoble-alpes.fr.

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Classifications MeSH