Efalizumab binding to the LFA-1 alpha(L) I domain blocks ICAM-1 binding via steric hindrance

	Efalizumab binding to the LFA-1 alpha(L) I domain blocks ICAM-1 binding via steric hindrance
	Li, S; Wang, H; Peng, BZ; Zhang, ML; Zhang, DP; Hou, S; Guo, YJ; Ding, JP
刊名	PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
	2009
卷号	106 期号:11 页码:4349-4354
通讯作者	Guo, YJ (reprint author), Second Mil Med Univ, Int Joint Canc Inst, 800 Xiang Yin Rd, Shanghai 200433, Peoples R China.,yjguo@smmu.edu.cn ; jpding@sibs.ac.cn
英文摘要	Lymphocyte function-associated antigen 1 (LFA-1) plays important roles in immune cell adhesion, trafficking, and activation and is a therapeutic target for the treatment of multiple autoimmune diseases. Efalizumab is one of the most efficacious antibody drugs for treating psoriasis, a very common skin disease, through inhibition of the binding of LFA-1 to the ligand intercellular adhesion molecule 1 (ICAM-1). We report here the crystal structures of the Efalizumab Fab alone and in complex with the LFA-1 alpha(L) I domain, which reveal the molecular mechanism of inhibition of LFA-1 by Efalizumab. The Fab binds with an epitope on the inserted (I) domain that is distinct from the ligand-binding site. Efalizumab binding blocks the binding of LFA-1 to ICAM-1 via steric hindrance between its light chain and ICAM-1 domain 2 and thus inhibits the activities of LFA-1. These results have important implications for the development of improved antibodies and new therapeutic strategies for the treatment of autoimmune diseases.
学科主题	Science & Technology - Other Topics
类目[WOS]	Multidisciplinary Sciences
关键词[WOS]	FUNCTION-ASSOCIATED ANTIGEN-1 ; INTERCELLULAR-ADHESION MOLECULE-1 ; CRYSTAL-STRUCTURE ; STRUCTURAL BASIS ; MONOCLONAL-ANTIBODIES ; INTEGRIN REGULATION ; LEUKOCYTE ADHESION ; INSERTED DOMAIN ; A-DOMAIN ; CD11A
收录类别	SCI
语种	英语
WOS记录号	WOS:000264278800054
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1259]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Li, S,Wang, H,Peng, BZ,et al. Efalizumab binding to the LFA-1 alpha(L) I domain blocks ICAM-1 binding via steric hindrance[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2009,106(11):4349-4354.
APA	Li, S.,Wang, H.,Peng, BZ.,Zhang, ML.,Zhang, DP.,...&Ding, JP.(2009).Efalizumab binding to the LFA-1 alpha(L) I domain blocks ICAM-1 binding via steric hindrance.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,106(11),4349-4354.
MLA	Li, S,et al."Efalizumab binding to the LFA-1 alpha(L) I domain blocks ICAM-1 binding via steric hindrance".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 106.11(2009):4349-4354.