De novo design of peptides targeted to the EF hands of calmodulin

Academic Article

Abstract

  • This report describes the use of the concept of inversion of hydropathy patterns to the de novo design of peptides targeted to a predetermined site on a protein. Eight- and 12-residue peptides were constructed with the EF hands or Ca2+-coordinating sites of calmodulin as their anticipated points of interaction. These peptides, but not unrelated peptides nor those with the same amino acid composition but a scrambled sequence, interacted with the two carboxyl-terminal Ca2+-binding sites of calmodulin as well as the EF hands of troponin C. The interactions resulted in a conformational change whereby the 8-mer peptide-calmodulin complex could activate phosphodiesterase in the absence of Ca2+. In contrast, the 12-mer peptide-calmodulin complex did not activate phosphodiesterase but rather inhibited activation by Ca2+. This inhibition could be overcome by high levels of Ca2+. Thus, it would appear that the aforementioned concept can be used to make peptide agonists and antagonists that are targeted to predetermined sites on proteins such as calmodulin.
  • Published In

    Digital Object Identifier (doi)

    Pubmed Id

  • 17366626
  • Author List

  • Villain M; Jackson PL; Manion MK; Dong WJ; Su Z; Fassina G; Johnson TM; Sakai TT; Krishna NR; Blalock JE
  • Start Page

  • 2676
  • End Page

  • 2685
  • Volume

  • 275
  • Issue

  • 4