Highly Ordered Protein Nanorings Designed by Accurate Control of Glutathione S‑Transferase Self-Assembly

• Published in: Journal of the American Chemical Society 2013-07, Vol.135 (30), p.10966-10969
• Main Authors: Bai, Yushi, Luo, Quan, Zhang, Wei, Miao, Lu, Xu, Jiayun, Li, Hongbin, Liu, Junqiu
• Format: Article
• Language: English
• Subjects: Animals; Chelating Agents - chemistry; Drug Design; Glutathione Transferase - chemistry; Nanostructures - chemistry; Protein Multimerization; Protein Structure, Quaternary; Schistosoma japonicum - enzymology
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja405519s

Protein self-assembly into exquisite, complex, yet highly ordered architectures represents the supreme wisdom of nature. However, precise manipulation of protein self-assembly behavior in vitro is a great challenge. Here we report that by taking advantage of the cooperation of metal-ion-chelating interactions and nonspecific protein–protein interactions, we achieved accurate control of the orientation of proteins and their self-assembly into protein nanorings. As a building block, we utilized the C 2-symmetric protein sjGST-2His, a variant of glutathione S-transferase from Schistosoma japonicum having two properly oriented His metal-chelating sites on the surface. Through synergic metal-coordination and non-covalent interactions, sjGST-2His self-assembled in a fixed bending manner to form highly ordered protein nanorings. The diameters of the nanorings can be regulated by tuning the strength of the non-covalent interaction network between sjGST-2His interfaces through variation of the ionic strength of the solution. This work provides a de novo design strategy that can be applied in the construction of novel protein superstructures.