Supramolecular protein glue to boost enzyme activity (original) (raw)

Abstract

Proteins possess many biological functions. However, they can easily degrade or aggregate, thus losing their bioactivity. Therefore, it is very important to develop materials capable of interacting with proteins and forming nanostructures for protein storage and delivery. In this study, we serendipitously found a novel peptide-based supramolecular protein glue (Nap-GFFYK(γE)2-NH2, compound 1) that could co-assemble with proteins into nanofibers and hydrogels. We found that compound 1 rapidly folded into a β-sheet conformation upon contact with many proteins but not with polymers. Total internal reflection fluorescence microscopy (TIRFM) images clearly show the formation of co-assembled nanofibers by proteins and the peptide. The supramolecular protein glue could improve the dispersion of enzymes (lipase and lysozyme) and therefore enhance their catalytic activity, especially at high temperatures. More importantly, the supramolecular protein glue could co-assemble with two enzymes, glucose oxidase/horseradish peroxidase (GOx/HRP) and GOx/cytochrome c (cyt c), to form nanofibers that significantly enhanced the catalytic activity of tandem enzymatic reactions. We envisioned the great potential of our supramolecular protein glue for protein storage, delivery, and bioactivity manipulation.

摘要

蛋白质具有许多生物学功能. 然而, 它们很容易降解和聚集, 从而失去其生物活性. 因此, 开发一种能够与蛋白质存在相互作用力的纳米材料对蛋白质的储存和递送是十分重要的. 在本研究中, 我们偶然发现了一个新奇的多肽超分子蛋白胶(Nap-GFFYK(γE)2-NH2, 化合物1), 可以与蛋白质共组装形成纳米纤维和水凝胶. 我们发现, 当化合物1接触到蛋白时会快速折叠形成β-折叠构象, 但与聚合物接触时未有这一现象. 全内反射荧光显微镜(TIRFM)图像清楚地显示了蛋白质和多肽通过共组装形成纳米纤维的过程. 我们还发现超分子蛋白胶改善了酶(脂肪酶和溶菌酶)的溶解性和分散性, 因此提高了它们(特别是在高温下)的催化活性. 更重要的是, 我们的超分子蛋白胶可以与两种酶(GOx/HRP或GOx/cyt c)共组装形成纳米纤维, 显著增强串联酶促反应的催化活性. 超分子蛋白胶在蛋白质储存、 传递和生物活性调控方面具有巨大潜力.

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Acknowledgements

This work was supported by the National Science Fund for Distinguished Young Scholars (31825012), the National Key Research and Development Program of China (2017YFC1103502), the National Natural Science Foundation of China (NSFC, 51773097, 51873156 and 21876116), Tianjin Science Fund for Distinguished Young Scholars (17JCJQJC44900), the National Program for Support of Topnotch Young Professionals, the Fundamental Research Funds for the Central Universities, and the Young Elite Scientists Sponsorship Program by Tianjin (TJSQNTJ-2017-16).

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Authors and Affiliations

  1. Key Laboratory of Bioactive Materials, Ministry of Education, State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin, 300071, China
    Yuna Shang (商宇娜), Zhongyan Wang (王忠彦), Jie Gao (高洁) & Zhimou Yang (杨志谋)
  2. School of Chemical Science and Engineering, Tongji University, Shanghai, 200092, China
    Yue Liao (廖悦) & Qigang Wang (王启刚)
  3. State Key Laboratory of Medicinal Chemical Biology, College of Chemistry, Nankai University, Tianjin, 300071, China
    Zhongju Ye (叶中菊) & Lehui Xiao (肖乐辉)

Authors

  1. Yuna Shang (商宇娜)
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  2. Yue Liao (廖悦)
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  3. Zhongju Ye (叶中菊)
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  4. Zhongyan Wang (王忠彦)
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  5. Lehui Xiao (肖乐辉)
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  6. Jie Gao (高洁)
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  7. Qigang Wang (王启刚)
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  8. Zhimou Yang (杨志谋)
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Corresponding authors

Correspondence toJie Gao (高洁), Qigang Wang (王启刚) or Zhimou Yang (杨志谋).

Additional information

Yuna Shang received her BSc from Hebei University in 2016. Then she continued her study as a PhD candidate in Prof. Zhimou Yang’s Lab in Nankai University. Her research interest mainly focuses on the growth factors mimic peptides and biohybrid hydrogels based on proteins and peptides.

Jie Gao obtained a BSc degree in materials science and engineering from Tianjin University in 2008, and a PhD degree in polymeric chemistry and physics from Nankai University in 2013. Then she joined the Faculty of Nankai University in 2013, and now she is an associate professor of biomaterials. Her research interest focuses on the development of novel supramolecular hydrogels for biomedical applications.

Qigang Wang received his BSc and MSc from the East China University of Science and Technology in 1999 and 2002, respectively. He obtained his PhD degree in 2005 from Shanghai Institute of Ceramics, CAS under the supervision of Prof. Qiuming Gao. Before starting his independent research at Tongji University in March 2011, he was a postdoctoral fellow with Prof. Takuzo Aida at Tokyo University and Prof. Bing Xu at Hong Kong University of Science and Technology. His research interests focus on the mild bio-oxidative preparation and biomedical application of enzymeladen hybrid hydrogel.

Zhimou Yang received his BSc from Nanjing University in 2001. He obtained his PhD degree in 2006 from Hong Kong University of Science and Technology under the supervision of Prof. Bing Xu. Before starting his independent research at Nankai University in March 2009, he was a postdoctoral fellow with Prof. Matthew Bogyo at Stanford Medical School. His research interests focus on molecular hydrogels of therapeutic agents (especially anti-cancer drugs) and short peptides and hydrogels based on protein-peptide interactions.

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Shang, Y., Liao, Y., Ye, Z. et al. Supramolecular protein glue to boost enzyme activity.Sci. China Mater. 62, 1341–1349 (2019). https://doi.org/10.1007/s40843-019-9425-6

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