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The dynamic organization of fungal acetyl-CoA carboxylase

DOI: 10.1038/ncomms11196 DOI Help

Authors: Moritz Hunkeler (University of Basel) , Edward Stuttfeld (University of Basel) , Anna Hagmann (University of Basel) , Stefan Imseng (University of Basel) , Timm Maier (University of Basel)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 7

State: Published (Approved)
Published: April 2016
Diamond Proposal Number(s): 12087 , 12133 , 14423

Open Access Open Access

Abstract: Acetyl-CoA carboxylases (ACCs) catalyse the committed step in fatty-acid biosynthesis: the ATP-dependent carboxylation of acetyl-CoA to malonyl-CoA. They are important regulatory hubs for metabolic control and relevant drug targets for the treatment of the metabolic syndrome and cancer. Eukaryotic ACCs are single-chain multienzymes characterized by a large, non-catalytic central domain (CD), whose role in ACC regulation remains poorly characterized. Here we report the crystal structure of the yeast ACC CD, revealing a unique four-domain organization. A regulatory loop, which is phosphorylated at the key functional phosphorylation site of fungal ACC, wedges into a crevice between two domains of CD. Combining the yeast CD structure with intermediate and low-resolution data of larger fragments up to intact ACCs provides a comprehensive characterization of the dynamic fungal ACC architecture. In contrast to related carboxylases, large-scale conformational changes are required for substrate turnover, and are mediated by the CD under phosphorylation control.

Subject Areas: Biology and Bio-materials

Instruments: B21-High Throughput SAXS

Other Facilities: Swiss Light Source

Added On: 17/06/2016 08:17

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