| Autor: |
Villain, Matteo, Jackson, Patricia L., Manion, Michael K., Dong, Wen-Ji, Su, Zhengchang, Fassina, Giorgio, Johnson, Tonny M., Sakai, Ted T., Krishna, N.Rama, Blalock, J.Edwin |
| Zdroj: |
Journal of Biological Chemistry; January 2000, Vol. 275 Issue: 4 p2676-2685, 10p |
| Abstrakt: |
This report describes the use of the concept of inversion of hydropathy patterns to the de novodesign 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. |
| Databáze: |
Supplemental Index |
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