title: The missing linker: a dimerization motif located within polyketide synthase modules.
abstract: The dimerization of multimodular polyketide synthases is essential for their function. Motifs that supplement the contacts made by dimeric polyketide synthase enzymes have previously been characterized outside the boundaries of modules, at the N- and C-terminal ends of polyketide synthase subunits. Here we describe a heretofore uncharacterized dimerization motif located within modules. The dimeric state of this dimerization element was elucidated through the 2.6 Å resolution crystal structure of a fragment containing a dimerization element and a ketoreductase. The solution structure of a standalone dimerization element was revealed by nuclear magnetic resonance spectroscopy to be consistent with that of the crystal structure, and its dimerization constant was measured through analytical ultracentrifugation to be ∼20 μM. The dimer buries ∼990 Å(2) at its interface, and its C-terminal helices rigidly connect to ketoreductase domains to constrain their locations within a module. These structural restraints permitted the construction of a common type of polyketide synthase module.
authors.affiliation: Department of Chemistry & Biochemistry, The University of Texas at Austin , 1 University Station A5300, Austin, Texas 78712, United States.
authors.forename: Jianting
authors.initials: J
authors.lastname: Zheng
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Fage
authors.forename: Borries
authors.initials: B
authors.lastname: Demeler
authors.forename: David W
authors.initials: DW
authors.lastname: Hoffman
authors.forename: Adrian T
authors.initials: AT
authors.lastname: Keatinge-Clay
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D008969:Molecular Sequence Data; D048630:Polyketide Synthases / Q000737:chemistry*; D011487:Protein Conformation; D055503:Protein Multimerization; D016930:Saccharopolyspora / Q000737:chemistry / Q000201:enzymology*
chemical_list: D048630:Polyketide Synthases