Department of Biotechnology, University of Verona, Strada Le Grazie, 15, 37134, Verona, Italy.
Chemistry. 2018 Apr 17;24(22):5911-5919. doi: 10.1002/chem.201705994. Epub 2018 Mar 23.
In biological systems, nanoparticles (NPs) elicit bioactivity upon interaction with proteins. As a result of post-translational modification, proteins occur in a variety of alternative covalent forms, including structural isomers, which present unique molecular surfaces. We aimed at a detailed description of the recognition of protein isomeric species by NP surfaces. The transient adsorption of isomeric ubiquitin (Ub) dimers by NPs was investigated by solution NMR spectroscopy. Lys63- and Lys48-linked Ub were adsorbed by large anionic NPs with different affinities, whereas the binding strength was similar in the cases of smaller particles. After the incorporation of paramagnetic tags into NPs, the observed site-resolved paramagnetic footprints provided a high-resolution map of the different protein surfaces binding to NPs. The approach described could be extended to further protein isoforms and more specialized NP systems to allow better control of the interactions between NPs and protein targets.
在生物系统中，纳米颗粒（NPs）与蛋白质相互作用会引发生物活性。由于翻译后修饰，蛋白质会以多种共价形式存在，包括结构异构体，它们具有独特的分子表面。我们旨在详细描述 NP 表面对蛋白质异构物种的识别。通过溶液 NMR 光谱研究了异构泛素（Ub）二聚体与 NPs 的瞬时吸附。大阴离子 NPs 以不同的亲和力吸附 Lys63-和 Lys48 连接的 Ub，而在较小颗粒的情况下，结合强度相似。在将顺磁标记物掺入 NPs 后，观察到的位点分辨顺磁足迹提供了与 NPs 结合的不同蛋白质表面的高分辨率图谱。所描述的方法可以扩展到进一步的蛋白质同工型和更专业的 NP 系统，以允许更好地控制 NPs 与蛋白质靶标的相互作用。
