Structure basis for AA98 inhibition on the activation of endothelial cells mediated by CD146

doi:10.1016/j.isci.2021.102417

HFCAS OpenIR

	Structure basis for AA98 inhibition on the activation of endothelial cells mediated by CD146
	Chen, Xuehui 1,2; Yan, Huiwen 3; Liu, Dan 1; Xu, Qingji 1,4; Duan, Hongxia 1; Feng, Jing 1; Yan, Xiyun 1,4; Xie, Can 2,5,6
	2021-05-21
发表期刊	ISCIENCE
通讯作者	Feng, Jing(fengjing@ibp.ac.cn) ; Yan, Xiyun(yanxy@ibp.ac.cn) ; Xie, Can(canxie@hmfl.ac.cn)
摘要	CD146 is an adhesion molecule that plays important roles in angiogenesis, cancer metastasis, and immune response. It exists as a monomer or dimer on the cell surface. AA98 is a monoclonal antibody that binds to CD146, which abrogates the activation of CD146-mediated signaling pathways and shows inhibitory effects on tumor growth. However, how AA98 inhibits the function of CD146 remains unclear. Here, we describe a crystal structure of the CD146/AA98 Fab complex at a resolution of 2.8 angstrom. Monomeric CD146 is stabilized by AA98 Fab binding to the junction region of CD146 domains 4 and 5. A higher-affinity AA98 variant (here named HA98) was thus rationally designed. Better binding to CD146 and prominent inhibition on cell migration were achieved with HA98. Further experiments on xenografted melanoma in mice with HA98 revealed superior inhibitory effects on tumor growth to those of AA98, which suggested future applications of this antibody in cancer therapy.
DOI	10.1016/j.isci.2021.102417
关键词[WOS]	ADHESION MOLECULE ; MONOCLONAL-ANTIBODY ; HUMAN-MELANOMA ; MCAM ; DIMERIZATION ; MUC18 ; RECEPTOR ; PROTEIN ; CANCER ; ANGIOGENESIS
收录类别	SCI
语种	英语
资助项目	National Natural Science Foundation of China[31770793] ; National Natural Science Foundation of China[31640001] ; National Natural Science Foundation of China[31370740] ; Hefei Institutes of Physical Science, Chinese Academy of Sciences[BJZX201901] ; Beijing Municipal Natural Science Foundation, China[7192123]
项目资助者	National Natural Science Foundation of China ; Hefei Institutes of Physical Science, Chinese Academy of Sciences ; Beijing Municipal Natural Science Foundation, China
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000653990500031
出版者	CELL PRESS
引用统计	被引频次：5[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.hfcas.ac.cn:8080/handle/334002/123751
专题	中国科学院合肥物质科学研究院
通讯作者	Feng, Jing; Yan, Xiyun; Xie, Can
作者单位	1.Chinese Acad Sci, Inst Biophys, Key Lab Prot & Peptide Pharmaceut, Beijing 100101, Peoples R China 2.Peking Univ, Sch Life Sci, State Key Lab Membrane Biol, Lab Mol Biophys, Beijing 100871, Peoples R China 3.Chinese Acad Sci, Inst Biophys, Key Lab RNA Biol, Beijing 100101, Peoples R China 4.Univ Chinese Acad Sci, Coll Life Sci, Beijing 100049, Peoples R China 5.Chinese Acad Sci, Hefei Inst Phys Sci, High Magnet Field Lab, Key Lab High Magnet Field & Ion Beam Phys Biol, Hefei 230031, Anhui, Peoples R China 6.Int Magnetobiol Frontier Res Ctr, Sci Isl, Hefei 230031, Peoples R China
推荐引用方式 GB/T 7714	Chen, Xuehui,Yan, Huiwen,Liu, Dan,et al. Structure basis for AA98 inhibition on the activation of endothelial cells mediated by CD146[J]. ISCIENCE,2021,24.
APA	Chen, Xuehui.,Yan, Huiwen.,Liu, Dan.,Xu, Qingji.,Duan, Hongxia.,...&Xie, Can.(2021).Structure basis for AA98 inhibition on the activation of endothelial cells mediated by CD146.ISCIENCE,24.
MLA	Chen, Xuehui,et al."Structure basis for AA98 inhibition on the activation of endothelial cells mediated by CD146".ISCIENCE 24(2021).