Affinity maturation of an antibody for the UV-induced DNA lesions 6,4 pyrimidine-pyrimidones

CORC > 生态环境研究中心 > 中国科学院生态环境研究中心 > 环境化学与生态毒理学国家重点实验室

	Affinity maturation of an antibody for the UV-induced DNA lesions 6,4 pyrimidine-pyrimidones
	Kong, Bingjie; Cao, Yang; Wu, Danni; An, Lili; Ran, Fanlei; Lin, Yan; Ye, Chen; Wang, Hailin; Hang, Haiying
刊名	APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
	2018-08-01
卷号	102 期号:15 页码:6409-6424
关键词	Antibody for DNA lesions Affinity maturation 6,4 Pyrimidine-pyrimidones (6-4PPs) DNA sequence-independent antibody
ISSN号	0175-7598
文献子类	Article
英文摘要	DNA lesions, associated mostly with minor changes in DNA structure, may induce permanent change in heritable coding information. Biochemically, these minor structural changes are difficult to be explored for generating high-affinity antibodies to detect specific DNA lesions in varying sequence contexts. Herein, we established a platform of bacterial display to facilitate antibodies to be matured with high affinity and high specificity against DNA lesions. To achieve this goal, we, for the first time, developed a two-round mutation/screening strategy: (1) using multiple lesion-containing DNA probes for primary maturation and (2) using single lesion-containing DNA probes for second maturation. Specifically, we capitalized on 64M-2 as a parental template to improve affinity for 6-4PP by 710-fold, compared with the model one. In addition, the matured antibody (9c3) is found to be much less dependent on the bases surrounding 6-4PPs than the model one. The mechanistic study from both computational simulation and reverse mutations revealed the critical roles of the two-round mutations in the enhanced binding affinity and independence of surrounding bases. This selection strategy opens a new way to improve affinity and specificity of antibodies for other DNA lesions.
内容类型	期刊论文
源URL	[http://ir.rcees.ac.cn/handle/311016/40869]
专题	生态环境研究中心_环境化学与生态毒理学国家重点实验室
推荐引用方式 GB/T 7714	Kong, Bingjie,Cao, Yang,Wu, Danni,et al. Affinity maturation of an antibody for the UV-induced DNA lesions 6,4 pyrimidine-pyrimidones[J]. APPLIED MICROBIOLOGY AND BIOTECHNOLOGY,2018,102(15):6409-6424.
APA	Kong, Bingjie.,Cao, Yang.,Wu, Danni.,An, Lili.,Ran, Fanlei.,...&Hang, Haiying.(2018).Affinity maturation of an antibody for the UV-induced DNA lesions 6,4 pyrimidine-pyrimidones.APPLIED MICROBIOLOGY AND BIOTECHNOLOGY,102(15),6409-6424.
MLA	Kong, Bingjie,et al."Affinity maturation of an antibody for the UV-induced DNA lesions 6,4 pyrimidine-pyrimidones".APPLIED MICROBIOLOGY AND BIOTECHNOLOGY 102.15(2018):6409-6424.