6CS9

Crystal structure of human beta-defensin 2 in complex with PIP2

Summary for 6CS9

• Entry DOI: 10.2210/pdb6cs9/pdb
• Descriptor: Beta-defensin 4A, [(2R)-2-octanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phosphoryl]oxy-propyl] octanoate (3 entities in total)
• Functional Keywords: antimicrobial, antifungal, defensin, innate defense, antimicrobial protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 10177.67

Authors

Jarva, M.,Phan, K.,Lay, F.T.,Humble, C.,Hulett, M.,Kvansakul, M. (deposition date: 2018-03-20, release date: 2018-07-25, Last modification date: 2024-11-20)

Primary citation

Jarva, M.,Phan, T.K.,Lay, F.T.,Caria, S.,Kvansakul, M.,Hulett, M.D.
Human beta-defensin 2 killsCandida albicansthrough phosphatidylinositol 4,5-bisphosphate-mediated membrane permeabilization.
Sci Adv, 4:eaat0979-eaat0979, 2018

PubMed 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 β-defensin 2 (HBD-2) permeabilizes cell membranes via a mechanism targeting the plasma membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP). We determined the structure of HBD-2 bound to PIP, which revealed two distinct PIP-binding sites, and showed, using functional assays, that mutations in these sites ablate PIP-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.

PubMed: 30050988
DOI: 10.1126/sciadv.aat0979

Experimental method

X-RAY DIFFRACTION (1.85 Å)