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Isoleucine/leucine(2) is essential for chemoattractant activity of beta-defensin Defb14 through chemokine receptor 6

Tyrrell, C; De Cecco, M; Reynolds, NL; Kilanowski, F; Campopiano, D; Barran, P; ... Dorin, JR; + view all (2010) Isoleucine/leucine(2) is essential for chemoattractant activity of beta-defensin Defb14 through chemokine receptor 6. MOL IMMUNOL , 47 (6) 1378 - 1382. 10.1016/j.molimm.2009.11.025.

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Abstract

beta-Defensins are both antimicrobial and able to chemoattract various immune cells including immature dendritic cells and CD4 T cells through CCR6. They are short, cationic peptides with a highly conserved six-cysteine motif. It has been shown that only the fifth cysteine is critical for chemoattraction of cells expressing CCR6. In order to identify other residues essential for functional interaction with CCR6 we used a library of peptide deletion derivatives based on Defb14. Loss of the initial two amino acids from the Defb14-1C(V) derivative destroys its ability to chemoattract cells expressing CCR6. As the second amino acid is an evolutionarily conserved leucine, we make full-length Defb14-1C(V) peptides with substitution of the leucine(2) for glycine (L2G), lysine (L2K) or isoleucine (L2I). Defb14-1C(V) L2G and L2K and are unable to chemoattract CCR6 expressing cells but the semi-conservative change L2I has activity. By circular dichroism spectroscopy we can see no evidence for a significant change in secondary structure as a consequence of these substitutions and so cannot attribute loss of chemotactic activity with disruption of the N-terminal helix. We conclude that isoleucine/leucine in the N-terminal alpha-helix region of this beta-defensin is essential for CCR6-mediated chemotaxis. (C) 2009 Elsevier Ltd. All rights reserved.

Type:Article
Title:Isoleucine/leucine(2) is essential for chemoattractant activity of beta-defensin Defb14 through chemokine receptor 6
DOI:10.1016/j.molimm.2009.11.025
Keywords:beta-Defensins, Chemotaxis, Defb14, hBD3, HUMAN BETA-DEFENSIN-3, CIRCULAR-DICHROISM, CYTOTOXICITY, CELLS, CCR6
UCL classification:UCL > School of BEAMS > Faculty of Maths and Physical Sciences > Chemistry

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