Multimeric options for the auto-activation of the Saccharomyces cerevisiae FAS type I megasynthase.
The fungal type I fatty acid synthase (FAS) is a 2.6 MDa multienzyme complex, catalyzing all necessary steps for the synthesis of long acyl chains. To be catalytically competent, the FAS must be activated by a posttranslational modification of the central acyl carrier domain (ACP) by an intrinsic phosphopantetheine transferase (PPT). However, recent X-ray structures of the fungal FAS revealed a barrel-shaped architecture, with PPT located at the outside of the barrel wall, spatially separated from the ACP caged in the inner volume. This separation indicated that the activation has to proceed before the assembly to the mature complex, in a conformation where the ACP and PPT domains can meet. To gain insight into the auto-activation reaction and also into the fungal FAS assembly pathway, we structurally and functionally characterized the Saccharomyces cerevisiae FAS type I PPT as part of the multienzyme protein and as an isolated domain.
Johansson
Patrik
P
Department of Membrane Biochemistry, Max-Planck-Institute of Biochemistry, Martinsried, Germany. johansso@biochem.mpg.de
Mulinacci
Barbara
B
Koestler
Caecilia
C
Vollrath
Ronnald
R
Oesterhelt
Dieter
D
Grininger
Martin
M
D000213:Acyl Carrier Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002384:Catalysis; D020134:Catalytic Domain; D003065:Coenzyme A / Q000737:chemistry / Q000378:metabolism; D004789:Enzyme Activation; D064429:Fatty Acid Synthases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism; D008274:Magnesium / Q000737:chemistry / Q000378:metabolism; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009154:Mutation; D011485:Protein Binding; D055503:Protein Multimerization; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D017855:Transferases (Other Substituted Phosphate Groups) / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D000213:Acyl Carrier Protein; D001426:Bacterial Proteins; D005227:Fatty Acids; D029701:Saccharomyces cerevisiae Proteins; C082662:phosphopantetheinyl transferase; D064429:Fatty Acid Synthases; D017855:Transferases (Other Substituted Phosphate Groups); C526685:FAS1 protein, S cerevisiae; D008274:Magnesium; D003065:Coenzyme A