Abstract.
The cathelin-like domain (CLD) of cathelicidins is grouped in the same superfamily with cystatins, natural cysteine protease inhibitors, due to their structural similarity. Intriguingly, human hCAP-18/LL37 and pig protegrin-3 (PG3) CLDs exhibit opposite effects against cathepsin L. Here, I evaluated the functional importance of the CLD through identifying whether positive selection has driven adaptive evolution of this domain. As a result, four positively selected sites were detected and three of them are located on a loop region previously recognized as a key determinant of the activating effect of the PG3 CLD. Analysis of amino acid variability of the CLD led to the discovery of a conserved region and three highly variable regions, in which two are subjected to positive selection. Positive selection targeting the variable regions provides a starting point for experimentally establishing a direct link between the observed amino acid changes and functional divergence of the CLD family.
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Received 8 February 2008; accepted 13 February 2008
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Zhu, S. Positive selection targeting the cathelin-like domain of the antimicrobial cathelicidin family. Cell. Mol. Life Sci. 65, 1285–1294 (2008). https://doi.org/10.1007/s00018-008-8070-x
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DOI: https://doi.org/10.1007/s00018-008-8070-x