4MTH

Crystal structure of mature human RegIIIalpha

4MTH の概要

• エントリーDOI: 10.2210/pdb4mth/pdb
• 分子名称: Regenerating islet-derived protein 3-alpha 15 kDa form, ZINC ION (3 entities in total)
• 機能のキーワード: hip/pap, regiii-gamma, c-type lectin, antimicrobial protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted: Q06141
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 15616.47

構造登録者

Derebe, M.G. (登録日: 2013-09-19, 公開日: 2013-11-27, 最終更新日: 2024-11-06)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.47 Å)