Role of the transmembrane domain in SNARE protein mediated membrane fusion: peptide nucleic acid/peptide model systems.
Role of the transmembrane domain in SNARE protein mediated membrane fusion: peptide nucleic acid/peptide model systems.
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跨膜结构域在 SNARE 蛋白介导的膜融合中的作用：肽核酸/肽模型系统
DOI：
10.1039/c6mb00294c
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发表时间：
2016
影响因子：
--
通讯作者：
R. Jahn U. Diederichsen
中科院分区：
文献类型：
--
作者：
J.-D. Wehland;A. S. Lygina;P. Kumar;S. Guha;B. E. Hubrich;R. Jahn U. Diederichsen
突触小泡与突触前质膜的融合是由可溶性 NSF（N-乙基马来酰亚胺敏感因子）附着蛋白受体蛋白（也称为 SNARE）介导的。这一基本过程的核心是将 SNARE 从相对的膜组装成紧密的四螺旋束，迫使膜紧密靠近。通过与 SNARE 类似但复杂性降低的模型系统，我们的目标是了解这些蛋白质如何在分子水平上发挥作用。在这里，肽核酸 (PNA) 被用作通过形成良好表征的双链体结构来模拟 SNARE 识别基序的优秀候选者。通过天然跨膜结构域 (TMD) 锚定在脂质体中的互补 PNA 链之间的杂交诱导参与囊泡的外小叶的合并，但不诱导内小叶的合并。提出了一系列 TMD 长度和 C 末端电荷不同的 PNA/肽杂合体。有趣的是，对于含有酰胺代替 C 末端天然羧酸的 TMD，可以看到外部和内部小叶的混合。 TMD C 末端的带电侧链对脂质体的混合有负面影响。 TMD 的长度对于融合至关重要，因为使用缩短的 TMD 可以完全阻止融合。
Fusion of synaptic vesicles with the presynaptic plasma membrane is mediated by Soluble NSF (N-ethylmaleimide-sensitive factor) Attachment Protein Receptor proteins also known as SNAREs. The backbone of this essential process is the assembly of SNAREs from opposite membranes into tight four helix bundles forcing membranes in close proximity. With model systems resembling SNAREs with reduced complexity we aim to understand how these proteins work at the molecular level. Here, peptide nucleic acids (PNAs) are used as excellent candidates for mimicking the SNARE recognition motif by forming well-characterized duplex structures. Hybridization between complementary PNA strands anchored in liposomes through native transmembrane domains (TMDs) induces the merger of the outer leaflets of the participating vesicles but not of the inner leaflets. A series of PNA/peptide hybrids differing in the length of TMDs and charges at the C-terminal end is presented. Interestingly, mixing of both outer and inner leaflets is seen for TMDs containing an amide in place of the natural carboxylic acid at the C-terminal end. Charged side chains at the C-terminal end of the TMDs are shown to have a negative impact on the mixing of liposomes. The length of the TMDs is vital for fusion as with the use of shortened TMDs, fusion was completely prevented.
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SNARE 蛋白亚型决定融合孔特征吗？
DOI：
10.1523/jneurosci.2087-15.2015
发表时间：
2015
期刊：
The Journal of Neuroscience
影响因子：
--
作者：
Linda van Keimpema;T. Kroon
通讯作者：
T. Kroon
影响因子：
2.1
作者：
Guha, Samit;Graf, Julia;Diederichsen, Ulf
通讯作者：
Diederichsen, Ulf
影响因子：
4.9
作者：
Kashiwada, Ayumi;Tsuboi, Mana;Matsuda, Kiyomi
通讯作者：
Matsuda, Kiyomi
影响因子：
2.9
作者：
STRUCK, DK;HOEKSTRA, D;PAGANO, RE
通讯作者：
PAGANO, RE
影响因子：
8.4
作者：
Fang, Qinghua;Lindau, Manfred
通讯作者：
Lindau, Manfred