Conformation-dependent antibacterial activity of the naturally occurring human peptide LL-37
Conformation-dependent antibacterial activity of the naturally occurring human peptide LL-37
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DOI：
10.1074/jbc.273.6.3718
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发表时间：
1998-02-06
影响因子：
4.8
通讯作者：
Agerberth, B
中科院分区：
文献类型：
--
作者：
Johansson, J;Gudmundsson, GH;Agerberth, B
研究了离子组成、pH 和肽浓度对 37 残基人抗菌肽 LL-37 的构象和活性的影响。在水中的微摩尔浓度下，LL-37 表现出与无序结构一致的圆二色光谱。添加 15 mM HCO3-、SO42- 或 CF3CO2- 会导致肽采用螺旋结构，效率大致相同，而 160 mM Cl- 效率较低。随着肽浓度增加，观察到从无序结构到螺旋结构的协同转变，与寡聚物的形成一致。α 螺旋度的程度与 LL-37 对革兰氏阳性菌和革兰氏阴性菌的抗菌活性相关。两种同源肽 FF-33 和 SK-29 分别在 N 末端含有 4 个和 8 个残基缺失，需要更高浓度的阴离子才能形成螺旋，并且对抗大肠杆菌 D21 的活性低于 LL 37。 pH低于5时，LL-37的螺旋含量逐渐减少，在pH 2时完全无序，相反，在pH超过13时，螺旋结构得以保留。LL-37对大肠杆菌的最小抑制浓度为5μM，在13-25μM时，该肽对多种真核细胞具有细胞毒性。在含有血浆、细胞内液或间质液的离子组合物的溶液中， LL-37 是螺旋状的，因此释放后可能对人体细胞造成危险。然而，在人血清存在下，LL-37 的抗菌和细胞毒活性受到抑制。
The influence of ion composition, pH, and peptide concentration on the conformation and activity of the 37-residue human antibacterial peptide LL-37 has been studied. At micromolar concentration in water, LL-37 exhibits a circular dichroism spectrum consistent with a disordered structure. The addition of 15 mM HCO3-, SO42-, or CF3CO2- causes the peptide to adopt a helical structure, with approximately equal efficiency, while 160 mM Cl- is less efficient, A cooperative transition from disordered to helical structure is observed as the peptide concentration is increased, consistent with formation of an oligomer, The extent of alpha-helicity correlates with the antibacterial activity of LL-37 against both Gram-positive and Gram-negative bacteria. Two homologous peptides, FF-33 and SK-29, containing 4 and 8 residue deletions at the N terminus, respectively, require higher concentrations of anions for helix formation and are less active than LL 37 against Escherichia coli D21. Below pH 5, the helical content of LL-37 gradually decreases, and at pH 2 it is entirely disordered, In contrast, the helical structure is retained at pH over 13. The minimal inhibitory concentration of LL-37 against E. coli is 5 mu M, and at 13-25 mu M the peptide is cytotoxic against several eukaryotic cells, In solutions containing the ion compositions of plasma, intracellular fluid, or interstitial fluid, LL-37 is helical, and hence it could pose a danger to human cells upon release. However, in the presence of human serum, the antibacterial and the cytotoxic activities of LL-37 are inhibited.