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Unifying themes in host defence effector polypeptides | Nature Reviews Microbiology
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The discovery of broad structural and functional relationships among host defence effector polypeptides from all biological kingdoms has provided new insights into the immunological roles of these molecules. This Opinion highlights the unifying themes of these host defence molecules by considering their evolutionary past and biomedical future. It is said that nature is the greatest innovator, yet molecular conservation can be equally powerful. One key requirement for the survival of any host is its ability to defend against infection, predation and competition. Recent discoveries, including the presence of a multidimensional structural signature, have revealed a previously unforeseen structural and functional congruence among host defence effector molecules spanning all kingdoms of life. Antimicrobial peptides, kinocidins, polypeptide venoms and other molecules that were once thought to be distinct in form and function now appear to be members of an ancient family of host defence effectors. These molecules probably descended from archetype predecessors that emerged during the beginning of life on earth. Understanding how nature has sustained these host defence molecules with a potent efficacy in the face of dynamic microbial evolution should provide new opportunities to prevent or treat life-threatening infections.
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nature portfolio permissions reprints privacy policy nf-κb nf-κb anti-candida activities multiple biological databases cardiovascular research center related human kinocidins advertising crotamine-related gene β-defensin antimicrobial-gene cluster social media personal data nature med toll-related receptors genome biol nature immunol data protection major-histocompatibility-complex molecules author information authors nature nature 439 tlr4 research c-terminal deletion products human lactoferrin-derived peptides protein secondary structure β-sheet forming tendencies author correspondence tlr-mediated inflammatory response normal t-cell expressed multidimensional γ-core signature springerlink instant access bovine β-defensin genes protein family treat life-threatening infections antibiotic-resistant infections human β-defensin-2 primate β-defensin genes deep generative models permissions de tomaso vitamin d-dependent mechanism accelerated antimicrobial discovery protein sci il-8 human cathelicidin peptides charge-neutralized propeptides antimicrobial host defence
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- Cationic defensins arise from charge-neutralized propeptides: a mechanism for avoiding leukocyte autocytotoxicity?
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