Cooperation between a T domain and a minimal C-terminal docking domain to enable specific assembly in a multiprotein NRPS

  • Non-ribosomal peptide synthetases (NRPS) produce natural products from amino acid building blocks. They often consist of multiple polypeptide chains which assemble in a specific linear order via specialized N- and C-terminal docking domains (N/CDDs). Typically, docking domains function independently from other domains in NRPS assembly. Thus, docking domain replacements enable the assembly of “designer” NRPS from proteins that normally do not interact. The multiprotein “peptide-antimicrobial-Xenorhabdus” (PAX) peptide-producing PaxS NRPS is assembled from the three proteins PaxA, PaxB and PaxC. Herein, we show that the small CDD of PaxA cooperates with its preceding thiolation (T1) domain to bind the NDD of PaxB with very high affinity, establishing a structural and thermodynamical basis for this unprecedented docking interaction, and we test its functional importance in vivo in a truncated PaxS assembly line. Similar docking interactions are apparently present in other NRPS systems.
Author:Jonas WatzelORCiDGND, Elke Duchardt-FernerORCiD, Sepas Sarawi, Helge Björn BodeORCiDGND, Jens WöhnertORCiDGND
Parent Title (German):Angewandte Chemie
Place of publication:Weinheim
Document Type:Article
Date of Publication (online):2021/04/19
Date of first Publication:2021/04/19
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2022/04/05
Tag:communication-mediating domains; docking domains; non-ribosomal peptide synthetase; peptide-antimicrobial-Xenorhabdus peptide; thiolation domain
Page Number:8
First Page:14171
Last Page:14178
All NMR measurements were carried out at the Center for Biomolecular Magnetic Resonance (BMRZ) at the Goethe University Frankfurt which is generously supported by the State of Hesse. This work was further supported by the LOEWE program of the state of Hesse and was conducted within the framework of the MegaSyn Research Cluster in the laboratories of H.B.B. and J.W. Work in the Bode lab is also supported by an ERC Advanced Grant (grant agreement number 835108). Open access funding enabled and organized by Projekt DEAL.
Wissenschaftliche Zentren und koordinierte Programme / Zentrum für Biomolekulare Magnetische Resonanz (BMRZ)
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Licence (German):License LogoCreative Commons - Namensnennung 4.0