Spontaneous formation of structurally diverse membrane channel architectures from a single antimicrobial peptide.
Spontaneous formation of structurally diverse membrane channel architectures from a single antimicrobial peptide.
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从单一抗菌肽自发形成结构多样的膜通道结构
DOI：
10.1038/ncomms13535
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发表时间：
2016-11-22
影响因子：
16.6
通讯作者：
Ulmschneider, Jakob P.
中科院分区：
文献类型：
--
作者：
Wang, Yukun;Chen, Charles H.;Hu, Dan;Ulmschneider, Martin B.;Ulmschneider, Jakob P.
许多抗菌肽（AMP）选择性地靶向微生物膜并在膜上形成孔。然而，膜靶向，孔形成和功能的机制仍然难以捉摸。在这里，我们报告了一个实验指导的无偏模拟方法，产生的AMP maculatin在原子分辨率的自发孔组装的机制。而不是一个单一的孔，maculatin形成一个结构多样的临时功能低聚孔，模仿完整的膜蛋白通道的结构。这些孔在膜中连续形成和解离。膜透化主要由六聚体、七聚体和八聚体控制，其传导水、离子和小染料。与目前的穿孔模型相反，孔通过将单个螺旋连续添加到跨膜螺旋或螺旋束而形成。由单一序列形成的孔结构的多样性可能是防止细菌耐药性的关键特征，并且可以解释为什么AMP中的序列-功能关系仍然难以捉摸。
Many antimicrobial peptides (AMPs) selectively target and form pores in microbial membranes. However, the mechanisms of membrane targeting, pore formation and function remain elusive. Here we report an experimentally guided unbiased simulation methodology that yields the mechanism of spontaneous pore assembly for the AMP maculatin at atomic resolution. Rather than a single pore, maculatin forms an ensemble of structurally diverse temporarily functional low-oligomeric pores, which mimic integral membrane protein channels in structure. These pores continuously form and dissociate in the membrane. Membrane permeabilization is dominated by hexa-, hepta- and octamers, which conduct water, ions and small dyes. Pores form by consecutive addition of individual helices to a transmembrane helix or helix bundle, in contrast to current poration models. The diversity of the pore architectures—formed by a single sequence—may be a key feature in preventing bacterial resistance and could explain why sequence–function relationships in AMPs remain elusive.
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影响因子：
3.3
作者：
Klauda, Jeffery B.;Venable, Richard M.;Freites, J. Alfredo;O'Connor, Joseph W.;Tobias, Douglas J.;Mondragon-Ramirez, Carlos;Vorobyov, Igor;MacKerell, Alexander D., Jr.;Pastor, Richard W.
通讯作者：
Pastor, Richard W.
影响因子：
3.4
作者：
Patel, Hiren;Tscheka, Clemens;Heerklotz, Heiko
通讯作者：
Heerklotz, Heiko
影响因子：
15
作者：
Ulmschneider, Jakob P.;Smith, Jeremy C.;White, Stephen H.;Ulmschneider, Martin B.
通讯作者：
Ulmschneider, Martin B.
DOI：
10.1002/jss.400020504
发表时间：
1974-01-01
期刊：
Journal of Supramolecular Structure
影响因子：
--
作者：
BAUMANN G;MUELLER P
通讯作者：
MUELLER P
影响因子：
15
作者：
Ulmschneider, Martin B.;Doux, Jacques P. F.;Ulmschneider, Jakob P.
通讯作者：
Ulmschneider, Jakob P.