Effects of Site-directed Mutagenesis of L469 in Helix-5 of Human Papillomavirus 16 L1 on Pentamer Formation

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	Effects of Site-directed Mutagenesis of L469 in Helix-5 of Human Papillomavirus 16 L1 on Pentamer Formation
其他题名	Effects of Site-directed Mutagenesis of L469 in Helix-5 of Human Papillomavirus 16 L1 on Pentamer Formation
	2017
发表期刊	CHEMICAL RESEARCH IN CHINESE UNIVERSITIES
ISSN	1005-9040
摘要	Located at the carboxyl terminal of the human papillomavirus major capsid protein L1, helix-5(h5) is crucial to L1 folding and pentamer formation. Site-directed mutagenesis of the leucine residue on site 469 into lysine, alanine, serine and glycine was performed to explore the effect of the resultant mutations on L1 pentamer formation. The soluble yields of the L1 pentamers of the L469A and L469K mutants were nearly two fold higher than that of the wild type. Molecular dynamics simulation was then performed to reveal the intrinsic mechanisms involved in the improvement of L1 pentamer yield. Accordingly, the secondary structures of h5, beta-G2, beta-B1, beta-C, beta-D, and beta-F were altered. The altered structures improved the hydrophobic interaction between h5 and beta-core "jelly" and the stability of h5. The hydrophobic surface area of residue 469 was reduced by 50% relative to that of the wild type. The C-O group of residue 469 and C-N group of L470 were both exposed to the solvent in the L469A mutant. These modifications may account for the increased solubility and stability and the promotion of pentamer formation induced by the point mutation. Therefore, the changes in the hydrophobic properties of h5 and the core structure determined the pentamer formation and solubility. This study may assist the development of a cost-effective platform for the production of prophylactic virus-like particle vaccines.
其他摘要	Located at the carboxyl terminal of the human papillomavirus major capsid protein L1, helix-5(h5) is crucial to L1 folding and pentamer formation. Site-directed mutagenesis of the leucine residue on site 469 into lysine, alanine, serine and glycine was performed to explore the effect of the resultant mutations on L1 pentamer formation. The soluble yields of the L1 pentamers of the L469A and L469K mutants were nearly two fold higher than that of the wild type. Molecular dynamics simulation was then performed to reveal the intrinsic mechanisms involved in the improvement of L1 pentamer yield. Accordingly, the secondary structures of h5, β-G2, β-Bl, β-C, β-D, and β-F were altered. The altered structures improved the hydrophobic interaction between h5 and β-core "jelly" and the stability of h5. The hydrophobic surface area of residue 469 was reduced by 50% relative to that of the wild type. The C--O group of residue 469 and C--N group of L470 were both exposed to the solvent in the L469A mutant. These modifications may account for the increased solubility and stability and the promotion of pentamer formation induced by the point mutation. Therefore, the changes in the hydrophobic properties of h5 and the core structure determined the pentamer formation and solubility. This study may assist the development of a cost-effective platform for the production of prophylactic virus-like particle vaccines.
关键词	VIRUS-LIKE PARTICLES CAPSID PROTEIN ESCHERICHIA-COLI EXPRESSION SIMULATIONS HPV ANTIBODIES INFECTION VACCINE WOMEN Human papillomavirus Capsid protein Helix-5 L1 pentamer
收录类别	CSCD
语种	英语
资助项目	[National Natural Science Foundation of China]
CSCD记录号	CSCD:6018841
引用统计
文献类型	期刊论文
条目标识符	http://ir.hfcas.ac.cn:8080/handle/334002/60537
专题	中国科学院合肥物质科学研究院
推荐引用方式 GB/T 7714	. Effects of Site-directed Mutagenesis of L469 in Helix-5 of Human Papillomavirus 16 L1 on Pentamer Formation[J]. CHEMICAL RESEARCH IN CHINESE UNIVERSITIES,2017,33.
APA	(2017).Effects of Site-directed Mutagenesis of L469 in Helix-5 of Human Papillomavirus 16 L1 on Pentamer Formation.CHEMICAL RESEARCH IN CHINESE UNIVERSITIES,33.
MLA	"Effects of Site-directed Mutagenesis of L469 in Helix-5 of Human Papillomavirus 16 L1 on Pentamer Formation".CHEMICAL RESEARCH IN CHINESE UNIVERSITIES 33(2017).