4MTH

Crystal structure of mature human RegIIIalpha

Summary for 4MTH

• Entry DOI: 10.2210/pdb4mth/pdb
• Descriptor: Regenerating islet-derived protein 3-alpha 15 kDa form, ZINC ION (3 entities in total)
• Functional Keywords: hip/pap, regiii-gamma, c-type lectin, antimicrobial protein
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: Q06141
• Total number of polymer chains: 1
• Total formula weight: 15616.47

Authors

Derebe, M.G. (deposition date: 2013-09-19, release date: 2013-11-27, Last modification date: 2024-11-06)

Primary citation

Mukherjee, S.,Zheng, H.,Derebe, M.G.,Callenberg, K.M.,Partch, C.L.,Rollins, D.,Propheter, D.C.,Rizo, J.,Grabe, M.,Jiang, Q.X.,Hooper, L.V.
Antibacterial membrane attack by a pore-forming intestinal C-type lectin.
Nature, 505:103-107, 2013

PubMed Abstract: 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.

PubMed: 24256734
DOI: 10.1038/nature12729

Experimental method

X-RAY DIFFRACTION (1.47 Å)