title: The bacterial signal transduction protein GlnB regulates the committed step in fatty acid biosynthesis by acting as a dissociable regulatory subunit of acetyl-CoA carboxylase.
abstract: Biosynthesis of fatty acids is one of the most fundamental biochemical pathways in nature. In bacteria and plant chloroplasts, the committed and rate-limiting step in fatty acid biosynthesis is catalyzed by a multi-subunit form of the acetyl-CoA carboxylase enzyme (ACC). This enzyme carboxylates acetyl-CoA to produce malonyl-CoA, which in turn acts as the building block for fatty acid elongation. In Escherichia coli, ACC is comprised of three functional modules: the biotin carboxylase (BC), the biotin carboxyl carrier protein (BCCP) and the carboxyl transferase (CT). Previous data showed that both bacterial and plant BCCP interact with signal transduction proteins belonging to the PII family. Here we show that the GlnB paralogues of the PII proteins from E. coli and Azospirillum brasiliense, but not the GlnK paralogues, can specifically form a ternary complex with the BC-BCCP components of ACC. This interaction results in ACC inhibition by decreasing the enzyme turnover number. Both the BC-BCCP-GlnB interaction and ACC inhibition were relieved by 2-oxoglutarate and by GlnB uridylylation. We propose that the GlnB protein acts as a 2-oxoglutarate-sensitive dissociable regulatory subunit of ACC in Bacteria.
authors.affiliation: Instituto Nacional de Ciência e Tecnologia da Fixação Biológica de Nitrogênio, Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, CEP 81531-990 CP 19046, Curitiba, PR, Brazil; Interfakultäres Institut für Mikrobiologie und Infektionsmedizin der Eberhard-Karls Universität Tübingen, Auf der Morgenstelle 28, Tübingen, 72076, Germany.
authors.forename: Edileusa C M
authors.initials: EC
authors.lastname: Gerhardt
authors.forename: Thiago E
authors.initials: TE
authors.lastname: Rodrigues
authors.forename: Marcelo
authors.initials: M
authors.lastname: Müller-Santos
authors.forename: Fabio O
authors.initials: FO
authors.lastname: Pedrosa
authors.forename: Emanuel M
authors.initials: EM
authors.lastname: Souza
authors.forename: Karl
authors.initials: K
authors.lastname: Forchhammer
authors.forename: Luciano F
authors.initials: LF
authors.lastname: Huergo
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000235:genetics* / Q000378:metabolism*; D015806:Azospirillum brasilense / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D019731:Carbon-Nitrogen Ligases / Q000378:metabolism; D019878:Carboxyl and Carbamoyl Transferases / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D054889:Fatty Acid Synthase, Type II / Q000235:genetics / Q000378:metabolism; D005227:Fatty Acids / Q000096:biosynthesis*; D009713:Nucleotidyltransferases / Q000235:genetics / Q000378:metabolism; D051922:PII Nitrogen Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D005227:Fatty Acids; C582443:GlnB protein, E coli; D051922:PII Nitrogen Regulatory Proteins; C404143:PIID regulatory protein, Bacteria; D019878:Carboxyl and Carbamoyl Transferases; C497878:glnK protein, E coli; D009713:Nucleotidyltransferases; D054889:Fatty Acid Synthase, Type II; D019731:Carbon-Nitrogen Ligases; C019791:biotin carboxylase; D000103:Acetyl-CoA Carboxylase; C079633:biotin carboxyl carrier protein