Fiche publication
Date publication
juillet 2024
Journal
RSC chemical biology
Auteurs
Membres identifiés du Cancéropôle Est :
Pr WEISSMAN Kira
Tous les auteurs :
Scat S, Weissman KJ, Chagot B
Lien Pubmed
Résumé
The fidelity of biosynthesis by modular polyketide synthases (PKSs) depends on specific moderate affinity interactions between successive polypeptide subunits mediated by docking domains (DDs). These sequence elements are notably portable, allowing their transplantation into alternative biosynthetic and metabolic contexts. Herein, we use integrative structural biology to characterize a pair of DDs from the toblerol -AT PKS. Both are intrinsically disordered regions (IDRs) that fold into a 3 α-helix docking complex of unprecedented topology. The C-terminal docking domain (DD) resembles the 4 α-helix type (4HB) DDs, which shows that the same type of DD can be redeployed to form complexes of distinct geometry. By carefully re-examining known DD structures, we further extend this observation to type 2 docking domains, establishing previously unsuspected structural relations between DD types. Taken together, these data illustrate the plasticity of α-helical DDs, which allow the formation of a diverse topological spectrum of docked complexes. The newly identified DDs should also find utility in modular PKS genetic engineering.
Référence
RSC Chem Biol. 2024 07 3;5(7):669-683
