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Schlagwörter:
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Zusammenfassung:
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/C)DDs). 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 (C)DD of PaxA cooperates with its preceding thiolation
(T-1) domain to bind the (DD)-D-N 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.
