Mechanism of action of a novel HD2 mutation

Leucocyte recruitment by redundant CC- and CXC-chemokines drives inflammation, playing a major role in atherosclerosis and aortic aneurysm. Ticks suppress inflammation using multi- chemokine-binding evasins, overcoming this redundancy. From one such evasin, we identified a hexadecapeptide HD2 that inhibits CC and CXC chemokines. Saturation mutagenesis revealed an HD2 mutant which exhibits surprisingly enhanced breadth and inhibitory potency. In this project  we will probe the mechanism of action and biophysical properties of this mutant peptide. These experiments would support the development of a novel approach to disrupt the chemokine network.

Model of HD2 peptide bound to the chemokine CCL8