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 i ntramolecular disulfide bonds and were homologous to RTD-1, a circular (the ta) defensin previously described by Tang et al. (Science, 286, 498-502, 19 99). However, whereas the 18 residues of RTD-1 represent spliced nonapeptid e fragments derived from two different demidefensin precursors, RTD-2 and - 3 comprise tandem nonapeptide repeats derived from only one of the RTD-1 pr ecursors. Thus, circular minidefensins are products of a novel posttranslat ional system that generates effector molecule diversity without commensurat e genome expansion. A system wherein two demidefensin genes can produce thr ee circular minidefensins might allow n such genes to produce (n/2)(n + 1) peptides.