Human ß-defensin 2 kills Candida albicans through phosphatidylinositol 4,5-bisphosphate-mediated membrane permeabilization.
Sci Adv
; 4(7): eaat0979, 2018 07.
Article
em En
| MEDLINE
| ID: mdl-30050988
ABSTRACT
Human defensins belong to a subfamily of the cationic antimicrobial peptides and act as a first line of defense against invading microbes. Their often broad-spectrum antimicrobial and antitumor activities make them attractive for therapeutic development; however, their precise molecular mechanism(s) of action remains to be defined. We show that human ß-defensin 2 (HBD-2) permeabilizes Candida albicans cell membranes via a mechanism targeting the plasma membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2). We determined the structure of HBD-2 bound to PIP2, which revealed two distinct PIP2-binding sites, and showed, using functional assays, that mutations in these sites ablate PIP2-mediated fungal growth inhibition by HBD-2. Our study provides the first insight into lipid-mediated human defensin membrane permeabilization at an atomic level and reveals a unique mode of lipid engagement to permeabilize cell membranes.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Candida albicans
/
Fosfatidilinositol 4,5-Difosfato
/
Beta-Defensinas
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article