title: Positive selection targeting the cathelin-like domain of the antimicrobial cathelicidin family.
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.
authors.affiliation: Group of Animal Innate Immunity, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Datun Road, Chaoyang District, Beijing, China. Zhusy@ioz.ac.cn
authors.forename: S
authors.initials: S
authors.lastname: Zhu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D054804:Cathelicidins / Q000737:chemistry* / Q000235:genetics*; D017124:Conserved Sequence; D020440:Gene Duplication; D006801:Humans; D016013:Likelihood Functions; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*; D012641:Selection, Genetic; D013552:Swine
chemical_list: D054804:Cathelicidins; D011506:Proteins; C084515:cathelin