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Analysis of the co-translational assembly of the fungal fatty acid synthase (FAS)

The yeast fatty acid synthase (FAS) is a barrel-shaped 2.6 MDa complex. Upon barrel-formation, two multidomain subunits, each more than 200 kDa large, intertwine to form a heterododecameric complex that buries 170,000 Å(2) of protein surface. In spite of the rich knowledge about yeast FAS in structu...

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Autores principales: Fischer, Manuel, Joppe, Mirko, Mulinacci, Barbara, Vollrath, Ronnald, Konstantinidis, Kosta, Kötter, Peter, Ciccarelli, Luciano, Vonck, Janet, Oesterhelt, Dieter, Grininger, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6972935/
https://www.ncbi.nlm.nih.gov/pubmed/31964902
http://dx.doi.org/10.1038/s41598-020-57418-8
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author Fischer, Manuel
Joppe, Mirko
Mulinacci, Barbara
Vollrath, Ronnald
Konstantinidis, Kosta
Kötter, Peter
Ciccarelli, Luciano
Vonck, Janet
Oesterhelt, Dieter
Grininger, Martin
author_facet Fischer, Manuel
Joppe, Mirko
Mulinacci, Barbara
Vollrath, Ronnald
Konstantinidis, Kosta
Kötter, Peter
Ciccarelli, Luciano
Vonck, Janet
Oesterhelt, Dieter
Grininger, Martin
author_sort Fischer, Manuel
collection PubMed
description The yeast fatty acid synthase (FAS) is a barrel-shaped 2.6 MDa complex. Upon barrel-formation, two multidomain subunits, each more than 200 kDa large, intertwine to form a heterododecameric complex that buries 170,000 Å(2) of protein surface. In spite of the rich knowledge about yeast FAS in structure and function, its assembly remained elusive until recently, when co-translational interaction of the β-subunit with the nascent α-subunit was found to initiate assembly. Here, we characterize the co-translational assembly of yeast FAS at a molecular level. We show that the co-translationally formed interface is sensitive to subtle perturbations, so that the exchange of two amino acids located in the emerging interface can prevent assembly. On the other hand, assembly can also be initiated via the co-translational interaction of the subunits at other sites, which implies that this process is not strictly site or sequence specific. We further highlight additional steps in the biogenesis of yeast FAS, as the formation of a dimeric subunit that orchestrates complex formation and acts as platform for post-translational phosphopantetheinylation. The presented data supports the understanding of the recently discovered prevalence of eukaryotic complexes for co-translational assembly, and is valuable for further harnessing FAS in the biotechnological production of aliphatic compounds.
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spelling pubmed-69729352020-01-27 Analysis of the co-translational assembly of the fungal fatty acid synthase (FAS) Fischer, Manuel Joppe, Mirko Mulinacci, Barbara Vollrath, Ronnald Konstantinidis, Kosta Kötter, Peter Ciccarelli, Luciano Vonck, Janet Oesterhelt, Dieter Grininger, Martin Sci Rep Article The yeast fatty acid synthase (FAS) is a barrel-shaped 2.6 MDa complex. Upon barrel-formation, two multidomain subunits, each more than 200 kDa large, intertwine to form a heterododecameric complex that buries 170,000 Å(2) of protein surface. In spite of the rich knowledge about yeast FAS in structure and function, its assembly remained elusive until recently, when co-translational interaction of the β-subunit with the nascent α-subunit was found to initiate assembly. Here, we characterize the co-translational assembly of yeast FAS at a molecular level. We show that the co-translationally formed interface is sensitive to subtle perturbations, so that the exchange of two amino acids located in the emerging interface can prevent assembly. On the other hand, assembly can also be initiated via the co-translational interaction of the subunits at other sites, which implies that this process is not strictly site or sequence specific. We further highlight additional steps in the biogenesis of yeast FAS, as the formation of a dimeric subunit that orchestrates complex formation and acts as platform for post-translational phosphopantetheinylation. The presented data supports the understanding of the recently discovered prevalence of eukaryotic complexes for co-translational assembly, and is valuable for further harnessing FAS in the biotechnological production of aliphatic compounds. Nature Publishing Group UK 2020-01-21 /pmc/articles/PMC6972935/ /pubmed/31964902 http://dx.doi.org/10.1038/s41598-020-57418-8 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Fischer, Manuel
Joppe, Mirko
Mulinacci, Barbara
Vollrath, Ronnald
Konstantinidis, Kosta
Kötter, Peter
Ciccarelli, Luciano
Vonck, Janet
Oesterhelt, Dieter
Grininger, Martin
Analysis of the co-translational assembly of the fungal fatty acid synthase (FAS)
title Analysis of the co-translational assembly of the fungal fatty acid synthase (FAS)
title_full Analysis of the co-translational assembly of the fungal fatty acid synthase (FAS)
title_fullStr Analysis of the co-translational assembly of the fungal fatty acid synthase (FAS)
title_full_unstemmed Analysis of the co-translational assembly of the fungal fatty acid synthase (FAS)
title_short Analysis of the co-translational assembly of the fungal fatty acid synthase (FAS)
title_sort analysis of the co-translational assembly of the fungal fatty acid synthase (fas)
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6972935/
https://www.ncbi.nlm.nih.gov/pubmed/31964902
http://dx.doi.org/10.1038/s41598-020-57418-8
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