Fiche publication
Date publication
mars 2016
Journal
Journal of the American Chemical Society
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GRUEZ Arnaud
,
Dr JACOB Christophe
,
Pr WEISSMAN Kira
Tous les auteurs :
Dorival J, Annaval T, Risser F, Collin S, Roblin P, Jacob C, Gruez A, Chagot B, Weissman KJ
Lien Pubmed
Résumé
Modular polyketide synthases (PKSs) direct the biosynthesis of clinically valuable secondary metabolites in bacteria. The fidelity of chain growth depends on specific recognition between successive subunits in each assembly line: interactions mediated by C- and N-terminal "docking domains" (DDs). We have identified a new family of DDs in trans-acyl transferase PKSs, exemplified by a matched pair from the virginiamycin (Vir) system. In the absence of C-terminal partner (VirA (C)DD) or a downstream catalytic domain, the N-terminal DD (VirFG (N)DD) exhibits multiple characteristics of an intrinsically disordered protein. Fusion of the two docking domains results in a stable fold for VirFG (N)DD and an overall protein-protein complex of unique topology whose structure we support by site-directed mutagenesis. Furthermore, using small-angle X-ray scattering (SAXS), the positions of the flanking acyl carrier protein and ketosynthase domains have been identified, allowing modeling of the complete intersubunit interface.
Mots clés
Acyltransferases, metabolism, Magnetic Resonance Spectroscopy, Models, Molecular, Polyketide Synthases, metabolism, Virginiamycin, chemistry
Référence
J. Am. Chem. Soc.. 2016 Mar;138(12):4155-67
