Evolution of the primate cathelicidin: Correlation between structural variations and antimicrobial activity

Igor Zelezetsky, Alessandra Pontillo, Luca Puzzi, Nikolinka Antcheva, Ludovica Segat, Sabrina Pacor, Sergio Crovella, Alessandro Tossi

Research output: Contribution to journalArticlepeer-review

Abstract

Cathelicidin genes homologous to the human CAMP gene, coding for the host defense peptide LL-37, have been sequenced and analyzed in 20 primate species, including Great Apes, hylobatidae, cercopithecidae, callithricidae, and cebidae. The region corresponding to the putative mature antimicrobial peptide is subject to a strong selective pressure for variation, with evidence for positive selection throughout the phylogenetic tree relating the peptides, which favors alterations in the charge while little affecting overall hydrophobicity or amphipathicity. Selected peptides were chemically synthesized and characterized, and two distinct types of behavior were observed. Macaque and leaf-eating monkey RL-37 peptides, like other helical antimicrobial peptides found in insect, frog, and mammalian species, were unstructured in bulk solution and had a potent, salt and medium independent antimicrobial activity in vitro, which may be the principal function also in vivo. Human LL-37 and the orangutan, hylobates, and callithrix homologues instead showed a salt-dependent structuring and likely aggregation in bulk solution that affected antimicrobial activity and its medium dependence. The two types of peptides differ also in their interaction with host cells. The evolution of these peptides has thus resulted in distinct mechanisms of action that affect the direct antimicrobial activity andmayalso modulate accessory antimicrobial functions due to interactions with host cells.

Original languageEnglish
Pages (from-to)19861-19871
Number of pages11
JournalJournal of Biological Chemistry
Volume281
Issue number29
DOIs
Publication statusPublished - Jul 21 2006

ASJC Scopus subject areas

  • Biochemistry

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