Direct structural analysis of a single acyl carrier protein domain in fatty acid synthase from the fungus Saccharomyces cerevisiae.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
12 Jan 2024
12 Jan 2024
Historique:
received:
24
07
2023
accepted:
03
01
2024
medline:
13
1
2024
pubmed:
13
1
2024
entrez:
12
1
2024
Statut:
epublish
Résumé
Acyl carrier protein (ACP) is the work horse of polyketide (PKS) and fatty acid synthases (FAS) and acts as a substrate shuttling domain in these mega enzymes. In fungi, FAS forms a 2.6 MDa symmetric assembly with six identical copies of FAS1 and FAS2 polypeptides. However, ACP spatial distribution is not restricted by symmetry owing to the long and flexible loops that tether the shuttling domain to its corresponding FAS2 polypeptide. This symmetry breaking has hampered experimental investigation of substrate shuttling route in fungal FAS. Here, we develop a protein engineering and expression method to isolate asymmetric fungal FAS proteins containing odd numbers of ACP domains. Electron cryomicroscopy (cryoEM) observation of the engineered complex reveals a non-uniform distribution of the substrate shuttling domain relative to its corresponding FAS2 polypeptide at 2.9 Å resolution. This work lays the methodological foundation for experimental study of ACP shuttling route in fungi.
Identifiants
pubmed: 38216676
doi: 10.1038/s42003-024-05777-7
pii: 10.1038/s42003-024-05777-7
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
92Informations de copyright
© 2024. The Author(s).
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