2K6O

Human LL-37 Structure

2K6O の概要

• エントリーDOI: 10.2210/pdb2k6o/pdb
• 関連するPDBエントリー: 2FBS 2FBU
• NMR情報: BMRB: 15876
• 分子名称: Cathelicidin antimicrobial peptide (1 entity in total)
• 機能のキーワード: human host defense peptide, human cathelicidin, antimicrobial peptide, ll-37, bacterial membrane targeting, antibiotic, antimicrobial, cleavage on pair of basic residues, pyrrolidone carboxylic acid, secreted, antimicrobial protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted: P49913
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 4504.35

構造登録者

Wang, G. (登録日: 2008-07-14, 公開日: 2008-09-23, 最終更新日: 2024-05-29)

主引用文献

Wang, G.
Structures of human host defense cathelicidin LL-37 and its smallest antimicrobial peptide KR-12 in lipid micelles
J.Biol.Chem., 283:32637-32643, 2008

PubMed Abstract: As a key component of the innate immunity system, human cathelicidin LL-37 plays an essential role in protecting humans against infectious diseases. To elucidate the structural basis for its targeting bacterial membrane, we have determined the high quality structure of (13)C,(15)N-labeled LL-37 by three-dimensional triple-resonance NMR spectroscopy, because two-dimensional (1)H NMR did not provide sufficient spectral resolution. The structure of LL-37 in SDS micelles is composed of a curved amphipathic helix-bend-helix motif spanning residues 2-31 followed by a disordered C-terminal tail. The helical bend is located between residues Gly-14 and Glu-16. Similar chemical shifts and (15)N nuclear Overhauser effect (NOE) patterns of the peptide in complex with dioctanoylphosphatidylglycerol (D8PG) micelles indicate a similar structure. The aromatic rings of Phe-5, Phe-6, Phe-17, and Phe-27 of LL-37, as well as arginines, showed intermolecular NOE cross-peaks with D8PG, providing direct evidence for the association of the entire amphipathic helix with anionic lipid micelles. The structure of LL-37 serves as a model for understanding the structure and function relationship of homologous primate cathelicidins. Using synthetic peptides, we also identified the smallest antibacterial peptide KR-12 corresponding to residues 18-29 of LL-37. Importantly, KR-12 displayed a selective toxic effect on bacteria but not human cells. NMR structural analysis revealed a short three-turn amphipathic helix rich in positively charged side chains, allowing for effective competition for anionic phosphatidylglycerols in bacterial membranes. KR-12 may be a useful peptide template for developing novel antimicrobial agents of therapeutic use.

PubMed: 18818205
DOI: 10.1074/jbc.M805533200

実験手法

SOLUTION NMR