Structure of a Synthetic Fragment of the LALF Protein When Bound to Lipopolysaccharide

Peptidic lipopolysaccharide (LPS) antagonists are the subject of intensive research. We report an NMR and modeling study of LALF-14 (GCKPTFRRLKWKYKCG), a synthetic cyclized fragment of the limulus anti-LPS factor (LALF) comprising residues 36?47. In a mixture with LPS we observed the transferred NOE effect and derived the LPS-bound structure of LALF-14. Neither the free nor the LPS-bound peptide displays NOEs indicative of a ��-sheet-like structure that is adopted by the fragment in the full-size protein. However, docking calculations show that the former structure is not a prerequisite for binding of LALF-14 to LPS.

肽类脂多糖（lipopolysaccharide, LPS）拮抗剂是当前备受关注的深入研究对象。本文报道了针对LALF-14（GCKPTFRRLKWKYKCG）的核磁共振（NMR）与建模研究：该片段为源自鲎抗LPS因子（limulus anti-LPS factor, LALF）36至47位氨基酸残基的合成环化肽段。在与LPS共孵育的混合体系中，我们观测到了转移核Overhauser效应（transferred NOE effect），并推导得到了LALF-14与LPS结合的复合物三维结构。无论是游离态还是与LPS结合的该肽段，均未呈现出指示类β折叠结构的NOE信号，而该折叠构象正是全长LALF中对应片段所采用的优势构象。然而，分子对接计算结果表明，该类β折叠构象并非LALF-14与LPS结合的必要前提。