Details
- Autor(en) / Beteiligte
- Titel
- Antibacterial membrane attack by a pore-forming intestinal C-type lectin
- Ist Teil von
- Nature (London), 2014-01, Vol.505 (7481), p.103-107
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2014
- Link zum Volltext
- Quelle
- EBSCOhost Psychology and Behavioral Sciences Collection
- Beschreibungen/Notizen
- Human body-surface epithelia coexist in close association with complex bacterial communities and are protected by a variety of antibacterial proteins. C-type lectins of the RegIII family are bactericidal proteins that limit direct contact between bacteria and the intestinal epithelium and thus promote tolerance to the intestinal microbiota. RegIII lectins recognize their bacterial targets by binding peptidoglycan carbohydrate, but the mechanism by which they kill bacteria is unknown. Here we elucidate the mechanistic basis for RegIII bactericidal activity. We show that human RegIIIα (also known as HIP/PAP) binds membrane phospholipids and kills bacteria by forming a hexameric membrane-permeabilizing oligomeric pore. We derive a three-dimensional model of the RegIIIα pore by docking the RegIIIα crystal structure into a cryo-electron microscopic map of the pore complex, and show that the model accords with experimentally determined properties of the pore. Lipopolysaccharide inhibits RegIIIα pore-forming activity, explaining why RegIIIα is bactericidal for Gram-positive but not Gram-negative bacteria. Our findings identify C-type lectins as mediators of membrane attack in the mucosal immune system, and provide detailed insight into an antibacterial mechanism that promotes mutualism with the resident microbiota.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0028-0836eISSN: 1476-4687DOI: 10.1038/nature12729Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4160023
- Format
- –
- Schlagworte
- Anti-Bacterial Agents - chemistry, Anti-Bacterial Agents - immunology, Anti-Bacterial Agents - metabolism, Anti-Bacterial Agents - pharmacology, Antigens, Neoplasm - chemistry, Antigens, Neoplasm - immunology, Antigens, Neoplasm - metabolism, Biological research, Biology, Experimental, Biomarkers, Tumor - antagonists & inhibitors, Biomarkers, Tumor - chemistry, Biomarkers, Tumor - immunology, Biomarkers, Tumor - metabolism, Cell Membrane Permeability - drug effects, Cryoelectron Microscopy, Crystallography, X-Ray, Gram-Negative Bacteria - drug effects, Gram-Negative Bacteria - immunology, Gram-Negative Bacteria - metabolism, Health aspects, Humans, Immunity, Mucosal - drug effects, Immunity, Mucosal - immunology, Intestines - chemistry, Intestines - immunology, Intestines - microbiology, Lectins, Lectins, C-Type - antagonists & inhibitors, Lectins, C-Type - chemistry, Lectins, C-Type - immunology, Lectins, C-Type - metabolism, Lipids, Lipopolysaccharides - pharmacology, Listeria, Listeria monocytogenes - drug effects, Listeria monocytogenes - immunology, Listeria monocytogenes - metabolism, Membranes, Membranes (Biology), Microbial Viability - drug effects, Microscopy, Models, Molecular, Pancreatitis-Associated Proteins, Peptidoglycan - metabolism, Phospholipids - metabolism, Physiological aspects, Pore size, Porins - antagonists & inhibitors, Porins - chemistry, Porins - metabolism, Proteins, Symbiosis