What determines the activity of antimicrobial and cytolytic peptides in model membranes.
What determines the activity of antimicrobial and cytolytic peptides in model membranes.
复制标题
DOI：
10.1021/bi200873u
复制
发表时间：
2011-09-20
期刊：
影响因子：
2.9
通讯作者：
Almeida, Paulo F.
中科院分区：
文献类型：
--
作者：
Clark, Kim S.;Svetlovics, James;McKeown, Alesia N.;Huskins, Laura;Almeida, Paulo F.
我们之前提出了三个假设，将模型膜中抗菌肽和溶细胞肽的机制与膜结合和插入膜的吉布斯自由能联系起来[Almeida，P.F.和Pokorny，A.(2009)BioChemical 48,8083-8093]。设计了两组多肽来验证这些假设，通过突变δ-赖氨酸、天蚕素A和Mainin 2的序列。在第一组中，通过将碱性残基突变为酸性残基或将碱性残基突变为酸性残基来改变多肽电荷，但氨基酸序列没有太大变化。根据预测，染料释放的类型从分级变为全或无。然而，以正确的间距在序列中定位带电残基以形成盐桥未能改善结合。在第二组中，带电残基和其他关键残基保持在相同的位置，而大部分序列被显著但保守地简化，保持了相同的疏水性和两亲性。这组数据的表现与预测完全不同。在天蚕素和美沙宁的突变体中，原本预计会保持的释放类型发生了戏剧性的变化，从全有或无变为分级。最后，与假设相反，结果表明，与膜结合的吉布斯能，而不是插入的吉布斯能，是多肽活性的主要决定因素。
We previously proposed three hypotheses relating the mechanism of antimicrobial and cytolytic peptides in model membranes to the Gibbs free energies of binding and insertion into the membrane [Almeida, P.F., and Pokorny, A. (2009) Biochemistry 48, 8083–8093]. Two sets of peptides were designed to test those hypotheses, by mutating the sequences of δ-lysin, cecropin A, and magainin 2. Peptide binding and activity were measured on phosphatidylcholine membranes. In the first set, the peptide charge was changed by mutating basic to acidic residues or vice versa, but the amino acid sequence was not altered much otherwise. The type of dye release changed from graded to all-or-none according to prediction. However, location of charged residues in the sequence with the correct spacing to form salt bridges failed to improve binding. In the second set, the charged and other key residues were kept in the same positions, whereas most of the sequence was significantly but conservatively simplified, maintaining the same hydrophobicity and amphipathicity. This set behaved completely different from predicted. The type of release, which was expected to be maintained, changed dramatically from all-or-none to graded in the mutants of cecropin and magainin. Finally, contrary to the hypotheses, the results indicate that the Gibbs energy of binding to the membrane, not the Gibbs energy of insertion, is the primary determinant of peptide activity.
登录
查看更多内容
影响因子：
3.4
作者：
Hällbrink, M;Florén, A;Langel, Ü
通讯作者：
Langel, Ü
影响因子：
3.4
作者：
Guarnera, Enrico;Pellarin, Riccardo;Caflisch, Amedeo
通讯作者：
Caflisch, Amedeo
影响因子：
3.1
作者：
KREGER, AS;KIM, KS;BERNHEIMER, AW
通讯作者：
BERNHEIMER, AW
影响因子：
3.4
作者：
Ladokhin, AS;Wimley, WC;White, SH
通讯作者：
White, SH
影响因子：
15
作者：
HAMMOND, GS
通讯作者：
HAMMOND, GS