title: Portability and Structure of the Four-Helix Bundle Docking Domains of trans-Acyltransferase Modular Polyketide Synthases.
abstract: The polypeptides of multimodular polyketide synthases self-assemble into biosynthetic factories. While the docking domains that mediate the assembly of cis-acyltransferase polyketide synthase polypeptides are well-studied, those of the more recently discovered trans-acyltransferase polyketide synthases have just started to be described. Located at the C- and N-termini of many polypeptides, these 25-residue, two-helix, pseudosymmetric motifs noncovalently connect domains both between and within modules. Domains expressed with their natural, cognate docking motifs formed complexes stable to size-exclusion chromatography with 1-10 μM dissociation constants as measured by isothermal titration calorimetry. Deletion and swapping experiments demonstrate portability of the docking motifs. A 1.72 Å-resolution structure of the N-terminal portion of the macrolactin synthase polypeptide MlnE shows an uncomplexed N-terminal docking motif to be preorganized in the conformation it assumes within the docking domain complex.
authors.affiliation: Department of Molecular Biosciences and ‡Department of Chemistry, The University of Texas at Austin , Austin, Texas 78712, United States.
authors.forename: Jia
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Department of Molecular Biosciences and ‡Department of Chemistry, The University of Texas at Austin , Austin, Texas 78712, United States.
authors.forename: Drew T
authors.initials: DT
authors.lastname: Wagner
authors.affiliation: Department of Molecular Biosciences and ‡Department of Chemistry, The University of Texas at Austin , Austin, Texas 78712, United States.
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Molecular Biosciences and ‡Department of Chemistry, The University of Texas at Austin , Austin, Texas 78712, United States.
authors.forename: Luisa
authors.initials: L
authors.lastname: Moretto
authors.affiliation: Department of Molecular Biosciences and ‡Department of Chemistry, The University of Texas at Austin , Austin, Texas 78712, United States.
authors.forename: Janci D
authors.initials: JD
authors.lastname: Addison
authors.affiliation: Department of Molecular Biosciences and ‡Department of Chemistry, The University of Texas at Austin , Austin, Texas 78712, United States.
authors.forename: Adrian T
authors.initials: AT
authors.lastname: Keatinge-Clay
mesh_terms: D000217:Acyltransferases / Q000737:chemistry*; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D048630:Polyketide Synthases / Q000737:chemistry*
chemical_list: D048630:Polyketide Synthases; D000217:Acyltransferases