Glycosylation of a Nonfibrillizing Appendage Alters the Self-Assembly Pathway of a Synthetic β-Sheet Fibrillizing Peptide.
Glycosylation of a Nonfibrillizing Appendage Alters the Self-Assembly Pathway of a Synthetic β-Sheet Fibrillizing Peptide.
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非纤维化肽的糖基化改变合成β折叠纤维化肽的自组装途径。
DOI：
10.1021/acs.jpcb.1c02083
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发表时间：
2021-06-24
影响因子：
3.3
通讯作者：
Hudalla, Gregory A.
中科院分区：
文献类型：
--
作者：
Zuo, Ran;Liu, Renjie;Olguin, Juanpablo;Hudalla, Gregory A.
由于它们的生物相容性和生物降解性，自组装成细长β-折叠纤维的短合成肽（即，肽纳米纤维）被广泛用于制造用于各种医学和生物技术应用的生物材料。糖基化，这是一种常见的蛋白质翻译后修饰，正在获得的兴趣，创造肽纳米纤维，可以模仿天然碳水化合物修饰的蛋白质的功能。最近的报道表明，糖基化可以破坏天然淀粉样蛋白形成肽的纤维化。在这里，使用透射电子显微镜，荧光显微镜，和硫磺素T光谱，我们表明，糖基化在一个网站外部的fifilizing域可以改变自组装途径的合成fifilizing肽，NSGSGQQKfifilizing FEQQ（NQ 11）。具体而言，用N-连接的N-乙酰葡糖胺修饰的NQ 11变体N（GlcNAc）SGSG-Q11（GQ 11）在去离子水（pH 5.8）中比NQ 11更慢地形成β-折叠纳米纤维，这与GQ 11形成短原纤维和非原纤维聚集体的组合的趋势相关，而NQ 11形成延伸的纳米纤维。酸性磷酸盐缓冲液减慢了GQ 11的絮凝速率并改变了所形成的结构的形态，但对NQ 11的絮凝速率或形态没有影响。缓冲液离子强度对两种肽的絮凝率没有影响，而二磷酸根阴离子对两种肽的絮凝率有类似的影响。总的来说，这些数据表明，位于β-折叠折叠结构域外部的聚糖部分可以改变合成肽的pH依赖性自组装途径，导致形成的结构的原纤维质量和形态的显著变化。这些观察结果增加了对糖基化对肽自组装的影响的理解，并应指导未来从合成β折叠折叠糖肽开发生物材料的努力。
Owing to their biocompatibility and biodegradability, short synthetic peptides that self-assemble into elongated β-sheet fibers (i.e., peptide nanofibers) are widely used to create biomaterials for diverse medical and biotechnology applications. Glycosylation, which is a common protein post-translational modification, is gaining interest for creating peptide nanofibers that can mimic the function of natural carbohydrate-modified proteins. Recent reports have shown that glycosylation can disrupt the fibrillization of natural amyloid-forming peptides. Here, using transmission electron microscopy, fluorescence microscopy, and thioflavin T spectroscopy we show that glycosylation at a site external to the fibrillization domain can alter the self-assembly pathway of a synthetic fibrillizing peptide, NSGSGQQKFQFQFEQQ (NQ11). Specifically, an NQ11 variant modified with N-linked N-acetylglucosamine, N(GlcNAc)SGSG-Q11 (GQ11), formed β-sheet nanofibers more slowly than NQ11 in deionized water (pH 5.8), which correlated with the tendency of GQ11 to form a combination of short fibrils and non-fibrillar aggregates, whereas NQ11 formed extended nanofibers. Acidic phosphate buffer slowed the rate of GQ11 fibrillization and altered the morphology of the structures formed, yet had no effect on NQ11 fibrillization rate or morphology. Buffer ionic strength had no effect on the fibrillization rate of either peptide, while diphosphate anion had a similar effect on the rate of fibrillization of both peptides. Collectively, these data demonstrate that a glycan moiety located external to the β-sheet fibrillizing domain can alter the pH-dependent self-assembly pathway of a synthetic peptide, leading to significant changes in the fibril mass and morphology of the structures formed. These observations add to the understanding of the effect of glycosylation on peptide self-assembly, and should guide future efforts to develop biomaterials from synthetic β-sheet fibrillizing glycopeptides.
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影响因子：
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