title: Ribonucleases as a host-defence family: evidence of evolutionarily conserved antimicrobial activity at the N-terminus.
abstract: Vertebrate secreted RNases (ribonucleases) are small proteins that play important roles in RNA metabolism, angiogenesis or host defence. In the present study we describe the antimicrobial properties of the N-terminal domain of the hcRNases (human canonical RNases) and show that their antimicrobial activity is well conserved among their lineage. Furthermore, all domains display a similar antimicrobial mechanism, characterized by bacteria agglutination followed by membrane permeabilization. The results of the present study show that, for all antimicrobial hcRNases, (i) activity is retained at the N-terminus and (ii) the antimicrobial mechanism is conserved. Moreover, using computational analysis we show that antimicrobial propensity may be conserved at the N-terminus for all vertebrate RNases, thereby suggesting that a defence mechanism could be a primary function in vertebrate RNases and that the N-terminus was selected to ensure this property. In a broader context, from the overall comparison of the peptides' physicochemical and biological properties, general correlation rules could be drawn to assist in the structure-based development of antimicrobial agents.
authors: *Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, 08193 Barcelona, Spain.
authors: Marc
authors: M
authors: Torrent
authors: David
authors: D
authors: Pulido
authors: Javier
authors: J
authors: Valle
authors: M Victòria
authors: MV
authors: Nogués
authors: David
authors: D
authors: Andreu
authors: Ester
authors: E
authors: Boix
mesh_terms: D000371:Agglutination; D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000276:immunology; D017124:Conserved Sequence; D019143:Evolution, Molecular; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000276:immunology; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000276:immunology; D006461:Hemolysis; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D008081:Liposomes / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010713:Phosphatidylcholines / Q000737:chemistry; D010715:Phosphatidylglycerols / Q000737:chemistry; D010802:Phylogeny; D012260:Ribonucleases / Q000737:chemistry* / Q000276:immunology / Q000502:physiology; D012756:Sheep
chemical_list: D023181:Antimicrobial Cationic Peptides; D008081:Liposomes; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; C051388:1,2-dioleoyl-sn-glycero-3-phosphoglycerol; D012260:Ribonucleases; C017251:1,2-oleoylphosphatidylcholine