Structural Characterization of the Cyclic Cystine
Ladder Motif of θ‑Defensins
- Publication date
- Publisher
Abstract
The θ-defensins are, to date,
the only known ribosomally
synthesized cyclic peptides in mammals, and they have promising antimicrobial
bioactivities. The characteristic structural motif of the θ-defensins
is the cyclic cystine ladder, comprising a cyclic peptide backbone
and three parallel disulfide bonds. In contrast to the cyclic cystine
knot, which characterizes the plant cyclotides, the cyclic cystine
ladder has not been as well described as a structural motif. Here
we report the solution structures and nuclear magnetic resonance relaxation
properties in aqueous solution of three representative θ-defensins
from different species. Our data suggest that the θ-defensins
are more rigid and structurally defined than previously thought. In
addition, all three θ-defensins were found to self-associate
in aqueous solution in a concentration-dependent and reversible manner,
a property that might have a role in their mechanism of action. The
structural definition of the θ-defensins and the cyclic cystine
ladder will help to guide exploitation of these molecules as structural
frameworks for the design of peptide drugs