Structural determinants of the eosinophil cationic protein antimicrobial activity

Ester Boix, Vivian A. Salazar, Marc Torrent, David Pulido, M. Victòria Nogués, Mohammed Moussaoui

Research output: Contribution to journalReview articleResearchpeer-review

32 Citations (Scopus)

Abstract

Antimicrobial RNases are small cationic proteins belonging to the vertebrate RNase A superfamily and endowed with a wide range of antipathogen activities. Vertebrate RNases, while sharing the active site architecture, are found to display a variety of noncatalytical biological properties, providing an excellent example of multitask proteins. The antibacterial activity of distant related RNases suggested that the family evolved from an ancestral host-defence function. The review provides a structural insight into antimicrobial RNases, taking as a reference the human RNase 3, also named eosinophil cationic protein (ECP). A particular high binding affinity against bacterial wall structures mediates the protein action. In particular, the interaction with the lipopolysaccharides at the Gram-negative outer membrane correlates with the protein antimicrobial and specific cell agglutinating activity. Although a direct mechanical action at the bacteria wall seems to be sufficient to trigger bacterial death, a potential intracellular target cannot be discarded. Indeed, the cationic clusters at the protein surface may serve both to interact with nucleic acids and cell surface heterosaccharides. Sequence determinants for ECP activity were screened by prediction tools, proteolysis and peptide synthesis. Docking results are complementing the structural analysis to delineate the protein anchoring sites for anionic targets of biological significance. Copyright © by Walter de Gruyter • Berlin • Boston.
Original languageEnglish
Pages (from-to)801-815
JournalBiological Chemistry
Volume393
Issue number8
DOIs
Publication statusPublished - 1 Aug 2012

Keywords

  • Bactericidal
  • Glycosaminoglycans
  • Host defence
  • Innate immunity
  • Nucleotides
  • RNase

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