Circular minidefensins and posttranslational generation of molecular diversity

We purified two new minidefensins (RTD‐2 and RTD‐3) from the bone marrow of rhesus monkeys. Both were circular octadecapeptides that contained three intramolecular disulfide bonds and were homologous to RTD‐1, a circular (θ) defensin previously described by Tang et al. (Science, 286, 498–502, 1999). However, whereas the 18 residues of RTD‐1 represent spliced nonapeptide fragments derived from two different demidefensin precursors, RTD‐2 and ‐3 comprise tandem nonapeptide repeats derived from only one of the RTD‐1 precursors. Thus, circular minidefensins are products of a novel posttranslational system that generates effector molecule diversity without commensurate genome expansion. A system wherein two demidefensin genes can produce three circular minidefensins might allow n such genes to produce (n/2)(n+1) peptides.