TY  - JOUR
A1  - Watzel, Jonas
A1  - Duchardt-Ferner, Elke
A1  - Sarawi, Sepas
A1  - Bode, Helge Björn
A1  - Wöhnert, Jens
T1  - Cooperation between a T domain and a minimal C-terminal docking domain to enable specific assembly in a multiprotein NRPS
T2  - Angewandte Chemie
N2  - 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.
KW  - communication-mediating domains
KW  - docking domains
KW  - non-ribosomal peptide synthetase
KW  - peptide-antimicrobial-Xenorhabdus peptide
KW  - thiolation domain
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/63888
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-638886
SN  - 1521-3773
N1  - 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.
VL  - 60
IS  - 25
SP  - 14171
EP  - 14178
PB  - Wiley-VCH
CY  - Weinheim
ER  -