The effect of graphene oxide on conformation change, aggregation and cytotoxicity of HIV-1 regulatory protein (Vpr)

• Published in: Biomaterials 2013-01, Vol.34 (4), p.1383-1390
• Main Authors: Zhang, Min, Mao, Xiaobo, Wang, Chenxuan, Zeng, Wenfeng, Zhang, Chunling, Li, Zhongjun, Fang, Ying, Yang, Yanlian, Liang, Wei, Wang, Chen
• Format: Article
• Language: English
• Subjects: Advanced Basic Science; Agglomeration; Aggregation; Assaying; Atomic structure; Cell Survival - drug effects; Conformation change; Cytotoxicity; Dentistry; Dichroism; Dimerization; Graphene; Graphene oxide; Graphite - chemistry; Graphite - toxicity; Human immunodeficiency virus; Human immunodeficiency virus 1; Hydrophobic interaction; Nanocapsules - chemistry; Nanocapsules - toxicity; Oxides; Oxides - chemistry; Oxides - toxicity; Protein Conformation; Proteins; Scanning tunneling microscopy; Surface chemistry; vpr Gene Products, Human Immunodeficiency Virus - toxicity; Vpr13-33
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2012.10.067

Abstract The fragment of viral protein R (Vpr), Vpr13-33, plays an important role in regulating nuclear importing of HIV through ion channel formation with a leucine-zipper-like α-helical conformation. Herein we report an approach to reduce cytotoxicity of Vpr13-33 by graphene oxide induced conformation change and aggregation. Preferential adsorption of Vpr13-33 on graphene oxide accompanied by conformation change from α-helix to β-sheet structures has been observed by using atomic force microscopy (AFM) and circular dichroism (CD). The submolecular structures of the Vpr13-33 peptide assembly on graphite surface have been identified by using scanning tunneling microscopy (STM), which confirms the β-sheet structures of Vpr13-33 on graphene oxide surface. The reduced cytotoxicity of Vpr13-33 to neuroblastoma cells and T cells are detected by MTT assay, which could be associated with the conformation change and stimulated aggregation of Vpr13-33 upon addition of graphene oxide through hydrophobic interaction. Furthermore, fluorescent leakage assay by using large unilamellar vesicles (LUVs) indicated that the GO reduced Vpr13-33-induced cytotoxicity could be associated with the inhibited “pore forming” function of Vpr13-33 by conformation change and aggregation.