Binding of diverse RiPP precursor peptides to their biosynthetic enzymes is mediated by a conserved domain related to the protein PqqD. A: Leader peptides of six different RiPP classes show diversity in leader peptide length and sequence composition. For microcin C7 and PQQ, the entire precursor protein is shown. The underlined segments in MccA, NisA, and PatE’ are portions of the peptide resolved in crystal structures of the precursors with their cognate biosynthetic enzymes. PQQ: pyrroloquinoline quinone, LAP: linear azoline. B: Superposition of the leader peptide-binding domains from MccB (red, PDB file 3H9G), NisB (blue, PDB file 4WD9), and LynD (orange, PDB file 4V1T). C: Comparison of leader peptide binding poses. MccB, NisB, and LynD are aligned as in part B, but only LynD is shown as gray mesh. The precursor peptides MccA (magenta), NisA (blue), and PatE’ (orange) are shown. The β-strands of NisA and PatE’ align with the β-strands of their cognate PqqD homolog.