title: Evidence for a protein-protein interaction motif on an acyl carrier protein domain from a modular polyketide synthase.
abstract: During biosynthesis on modular polyketide synthases (PKSs), chain extension intermediates are tethered to acyl carrier protein (ACP) domains through phosphopantetheinyl prosthetic groups. Each ACP must therefore interact with every other domain within the module, and also with a downstream acceptor domain. The nature of these interactions is key to our understanding of the topology and operation of these multienzymes. Sequence analysis and homology modeling implicates a potential helical region (helix II) on the ACPs as a protein-protein interaction motif. Using site-directed mutagenesis, we show that residues along this putative helix lie at the interface between the ACP and the phosphopantetheinyl transferase that catalyzes its activation. Our results accord with previous studies of discrete ACP proteins from fatty acid and aromatic polyketide biosynthesis, suggesting that helix II may also serve as a universal interaction motif in modular PKSs.
authors.affiliation: Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, United Kingdom. kjw21@cus.cam.ac.uk
authors.forename: Kira J
authors.initials: KJ
authors.lastname: Weissman
authors.forename: Hui
authors.initials: H
authors.lastname: Hong
authors.forename: Bojana
authors.initials: B
authors.lastname: Popovic
authors.forename: Filip
authors.initials: F
authors.lastname: Meersman
mesh_terms: D000213:Acyl Carrier Protein / Q000737:chemistry* / Q000378:metabolism*; D020816:Amino Acid Motifs; D001412:Bacillus subtilis / Q000201:enzymology / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D017124:Conserved Sequence; D004917:Erythromycin / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D048630:Polyketide Synthases / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D040681:Structural Homology, Protein; D017855:Transferases (Other Substituted Phosphate Groups) / Q000235:genetics / Q000378:metabolism
chemical_list: D000213:Acyl Carrier Protein; D001426:Bacterial Proteins; C082662:phosphopantetheinyl transferase; D004917:Erythromycin; D048630:Polyketide Synthases; D017855:Transferases (Other Substituted Phosphate Groups)