Peptidase Activation by a Leader Peptide-Bound RiPP Recognition Element.

ABSTRACT: The RiPP precursor recognition element (RRE) is a conserved domain found in many prokaryotic ribosomally synthesized and post-translationally modified peptide (RiPP) biosynthetic gene clusters (BGCs). RREs bind with high specificity and affinity to a recognition sequence within the N-terminal leader region of RiPP precursor peptides. Lasso peptide biosynthesis involves an RRE-dependent leader peptidase, which is discretely encoded or fused to the RRE as a di-domain protein. Here we leveraged thousands of predicted BGCs to define the RRE:leader peptidase interaction through evolutionary covariance analysis. Each interacting domain contributes a three-stranded β-sheet to form a hydrophobic β-sandwich-like interface. The bioinformatics-guided predictions were experimentally confirmed using pr

SUBMITTER: Kretsch AM 

PROVIDER: S-EPMC10126823 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature