Department of Biochemistry and Molecular Biology and the Structural Biology Center, University of Texas, Houston Medical School, Houston, Texas 77030, USA.
PEP-19 is a small calmodulin (CaM)-binding protein that greatly increases the rates of association and dissociation of Ca(2+) from the C-domain of CaM, an effect that is mediated by an acidic/IQ sequence in PEP-19. We show here using NMR that PEP-19 is an intrinsically disordered protein, but with residual structure localized to its acidic/IQ motif. We also show that the k(on) and k(off) rates for binding PEP-19 to apo-CaM are at least 50-fold slower than for binding to Ca(2+)-CaM. These data indicate that intrinsic disorder confers plasticity that allows PEP-19 to bind to either apo- or Ca(2+)-CaM via different structural modes, and that complex formation may be facilitated by conformational selection of residual structure in the acidic/IQ sequence.