Molecular basis for the recognition of CCN1 by monoclonal antibody 093G9

doi:10.1002/jmr.2645

	Molecular basis for the recognition of CCN1 by monoclonal antibody 093G9
	Zhong, Chen 1; Huo, Rongfen 2,3; Hu, Kuan 1; Shen, Jinlong 1; Li, Dangsheng 1; Li, Ningli 2,3; Ding, Jianping1,4,5
	2017-11
发表期刊	JOURNAL OF MOLECULAR RECOGNITION (IF:2.3[JCR-2023],2.2[5-Year])
ISSN	0952-3499
卷号	30 期号:11
发表状态	已发表
DOI	10.1002/jmr.2645
摘要	CCN1, also named Cyr61 (cysteine-rich protein 61), is the first identified member of the CCN family that is composed of 6 secreted extracellular matrix-associated glycoproteins. CCN1 has been demonstrated to participate in pathogenesis of rheumatoid arthritis through various pathways. A monoclonal antibody, namely, 093G9, is effective to antagonize the effects of CCN1 and hence has potential therapeutic benefits against rheumatoid arthritis. Here, we show that the epitope recognized by 093G9 is mapped to residues 77 to 80 of CCN1, and a cyclic peptide encompassing residues 75 to 81 of CCN1 displays high binding affinity for 093G9. The crystal structure of the 093G9 Fab in complex with the cyclic peptide was determined at 2.7 angstrom resolution, which reveals the intensive interactions between CCN1 and 093G9. Particularly, residues Asn79 and Phe80 of CCN1 are inserted into cavities mainly formed by residues of complementarity-determining region loop L3 and framework region L2 and by residues of complementarity-determining region loops H2 and H3, respectively, which contribute most of the interactions and therefore are critical for the recognition by 093G9. Together, these findings not only identify the epitope of CCN1 for 093G9 but also reveal the molecular mechanism of recognition and binding of CCN1 by 093G9.
关键词	CCN1 crystal structure epitope rheumatoid arthritis therapeutic antibody
收录类别	SCI
语种	英语
资助项目	Education Ministry Research Fund for the Doctoral Program[20130073110003]
WOS研究方向	Biochemistry & Molecular Biology ; Biophysics
WOS类目	Biochemistry & Molecular Biology ; Biophysics
WOS记录号	WOS:000412539400005
出版者	WILEY
WOS关键词	FIBROBLAST-LIKE SYNOVIOCYTES ; IMMEDIATE-EARLY GENE ; BREAST-CANCER ; RHEUMATOID-ARTHRITIS ; MATRICELLULAR PROTEIN ; ENDOTHELIAL-CELLS ; GROWTH-FACTOR ; BINDING-SITE ; CYR61 ; EXPRESSION
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/9924
专题	生命科学与技术学院_特聘教授组_丁建平组
通讯作者	Li, Ningli; Ding, Jianping
作者单位	1.Chinese Acad Sci, Natl Ctr Prot Sci Shanghai, State Key Lab Mol Biol,Shanghai Inst Biol Sci, Ctr Excellence Mol Cell Sci,Inst Biochem & Cell B, 320 Yue Yang Rd, Shanghai 200031, Peoples R China 2.Shanghai Jiao Tong Univ, Sch Med, Shanghai Inst Immunol, 280 South Chongqing Rd, Shanghai, Peoples R China 3.Shanghai Jiao Tong Univ, Sch Med, Dept Immunol & Microbiol, 280 South Chongqing Rd, Shanghai, Peoples R China 4.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 5.Chinese Acad Sci, Shanghai Sci Res Ctr, Shanghai, Peoples R China
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Zhong, Chen,Huo, Rongfen,Hu, Kuan,et al. Molecular basis for the recognition of CCN1 by monoclonal antibody 093G9[J]. JOURNAL OF MOLECULAR RECOGNITION,2017,30(11).
APA	Zhong, Chen.,Huo, Rongfen.,Hu, Kuan.,Shen, Jinlong.,Li, Dangsheng.,...&Ding, Jianping.(2017).Molecular basis for the recognition of CCN1 by monoclonal antibody 093G9.JOURNAL OF MOLECULAR RECOGNITION,30(11).
MLA	Zhong, Chen,et al."Molecular basis for the recognition of CCN1 by monoclonal antibody 093G9".JOURNAL OF MOLECULAR RECOGNITION 30.11(2017).