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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.
Afiliación
  • Fischer M; Institute of Organic Chemistry and Chemical Biology, Buchmann Institute for Molecular Life Sciences, Goethe University Frankfurt, Max-von-Laue-Str. 15, 60438, Frankfurt am Main, Germany.
  • Joppe M; Institute of Organic Chemistry and Chemical Biology, Buchmann Institute for Molecular Life Sciences, Goethe University Frankfurt, Max-von-Laue-Str. 15, 60438, Frankfurt am Main, Germany.
  • Mulinacci B; Department of Membrane Biochemistry, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152, Martinsried, Germany.
  • Vollrath R; Department of Membrane Biochemistry, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152, Martinsried, Germany.
  • Konstantinidis K; Department of Membrane Biochemistry, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152, Martinsried, Germany.
  • Kötter P; Institute of Molecular Genetics and Cellular Microbiology, Goethe University Frankfurt, Max-von-Laue-Str. 9, 60438, Frankfurt am Main, Germany.
  • Ciccarelli L; Department of Structural Biology, Max Planck Institute of Biophysics, Max-von-Laue-Str. 3, 60438, Frankfurt am Main, Germany.
  • Vonck J; Department of Structural Biology, Max Planck Institute of Biophysics, Max-von-Laue-Str. 3, 60438, Frankfurt am Main, Germany.
  • Oesterhelt D; Department of Membrane Biochemistry, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152, Martinsried, Germany.
  • Grininger M; Institute of Organic Chemistry and Chemical Biology, Buchmann Institute for Molecular Life Sciences, Goethe University Frankfurt, Max-von-Laue-Str. 15, 60438, Frankfurt am Main, Germany. grininger@chemie.uni-frankfurt.de.
Sci Rep ; 10(1): 895, 2020 01 21.
Article en En | MEDLINE | ID: mdl-31964902
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 Å2 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 ß-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.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de Saccharomyces cerevisiae / Ácido Graso Sintasas Tipo de estudio: Risk_factors_studies Idioma: En Revista: Sci Rep Año: 2020 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de Saccharomyces cerevisiae / Ácido Graso Sintasas Tipo de estudio: Risk_factors_studies Idioma: En Revista: Sci Rep Año: 2020 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido