Intramembrane ionic protein-lipid interaction regulates integrin structure and function

doi:10.1371/journal.pbio.2006525

	Intramembrane ionic protein-lipid interaction regulates integrin structure and function
	Chen, Jianfeng 3; Guo, Jun 2; Zhang, Youhua 1,3; Li, Hua 2; Chu, Huiying 4; Wang, Qinshu 5; Jiang, Shutan 2; Li, Yan 4; Shen, Hongbin 6; Li, Guohui 4
刊名	PLOS BIOLOGY
	2018-11-01
卷号	16 期号:11 页码:28
ISSN号	1545-7885
DOI	10.1371/journal.pbio.2006525
通讯作者	Li, Guohui(ghli@dicp.ac.cn) ; Chen, Jianfeng(jfchen@sibcb.ac.cn) ; Xu, Chenqi(cqxu@sibcb.ac.cn)
英文摘要	Protein transmembrane domains (TMDs) are generally hydrophobic, but our bioinformatics analysis shows that many TMDs contain basic residues at terminal regions. Physiological functions of these membrane-snorkeling basic residues are largely unclear. Here, we show that a membrane-snorkeling Lys residue in integrin alpha L beta 2 (also known as lymphocyte function-associated antigen 1 [LFA-1]) regulates transmembrane heterodimer formation and integrin adhesion through ionic interplay with acidic phospholipids and calcium ions (Ca2+) in T cells. The amino group of the conserved Lys ionically interacts with the phosphate group of acidic phospholipids to stabilize alpha L beta 2 transmembrane association, thus keeping the integrin at low-affinity conformation. Intracellular Ca2+ uses its charge to directly disrupt this ionic interaction, leading to the transmembrane separation and the subsequent extracellular domain extension to increase adhesion activity. This Ca2+-mediated regulation is independent on the canonical Ca2+ signaling or integrin inside-out signaling. Our work therefore showcases the importance of intramembrane ionic protein-lipid interaction and provides a new mechanism of integrin activation.
资助项目	CAS[XDB08020100] ; CAS[XDB29000000] ; CAS[QYZDB-SSW-SMC048] ; NSFC[31530022] ; NSFC[31425009] ; NSFC[31621003] ; NSFC[31525016] ; NSFC[31830112] ; NSFC[31471309] ; NSFC[81702309] ; NSFC[21625302] ; NSFC[21573217] ; STCSM[16JC1404800] ; Ten Thousand Talent Program National Program for Support of Top-notch Young Professionals of China ; Personalized Medicines-Molecular Signature-based Drug Discovery and Development ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12010101] ; MOST[2014CB541903]
WOS关键词	T-CELL-ACTIVATION ; PLASMA-MEMBRANE ; DYNAMICS ; BINDING ; LFA-1 ; ALPHA-IIB-BETA-3 ; LYMPHOCYTES ; PERFORMANCE ; SELECTIVITY ; SYNAPSE
WOS研究方向	Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics
语种	英语
出版者	PUBLIC LIBRARY SCIENCE
WOS记录号	WOS:000452442600009
资助机构	CAS ; CAS ; NSFC ; NSFC ; STCSM ; STCSM ; Ten Thousand Talent Program National Program for Support of Top-notch Young Professionals of China ; Ten Thousand Talent Program National Program for Support of Top-notch Young Professionals of China ; Personalized Medicines-Molecular Signature-based Drug Discovery and Development ; Personalized Medicines-Molecular Signature-based Drug Discovery and Development ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; MOST ; MOST ; CAS ; CAS ; NSFC ; NSFC ; STCSM ; STCSM ; Ten Thousand Talent Program National Program for Support of Top-notch Young Professionals of China ; Ten Thousand Talent Program National Program for Support of Top-notch Young Professionals of China ; Personalized Medicines-Molecular Signature-based Drug Discovery and Development ; Personalized Medicines-Molecular Signature-based Drug Discovery and Development ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; MOST ; MOST ; CAS ; CAS ; NSFC ; NSFC ; STCSM ; STCSM ; Ten Thousand Talent Program National Program for Support of Top-notch Young Professionals of China ; Ten Thousand Talent Program National Program for Support of Top-notch Young Professionals of China ; Personalized Medicines-Molecular Signature-based Drug Discovery and Development ; Personalized Medicines-Molecular Signature-based Drug Discovery and Development ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; MOST ; MOST ; CAS ; CAS ; NSFC ; NSFC ; STCSM ; STCSM ; Ten Thousand Talent Program National Program for Support of Top-notch Young Professionals of China ; Ten Thousand Talent Program National Program for Support of Top-notch Young Professionals of China ; Personalized Medicines-Molecular Signature-based Drug Discovery and Development ; Personalized Medicines-Molecular Signature-based Drug Discovery and Development ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; MOST ; MOST
内容类型	期刊论文
源URL	[http://cas-ir.dicp.ac.cn/handle/321008/166168]
专题	大连化学物理研究所_中国科学院大连化学物理研究所
通讯作者	Chen, Jianfeng; Li, Guohui; Xu, Chenqi
作者单位	1.Tongji Univ, Shanghai Peoples Hosp 10, Dept Pathol, Sch Med, Shanghai, Peoples R China 2.Univ Chinese Acad Sci, State Key Lab Mol Biol, Shanghai Sci Res Ctr,CAS Ctr Excellence Mol Cell, Shanghai Inst Biochem & Cell Biol,Chinese Acad Sc, Shanghai, Peoples R China 3.Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci, Shanghai Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai, Peoples R China 4.Chinese Acad Sci, State Key Lab Mol React Dynam, Dalian Inst Chem Phys, Lab Mol Modeling & Design, Dalian, Liaoning, Peoples R China 5.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 6.Shanghai Jiao Tong Univ, Inst Image Proc & Pattern Recognit, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	Chen, Jianfeng,Guo, Jun,Zhang, Youhua,et al. Intramembrane ionic protein-lipid interaction regulates integrin structure and function[J]. PLOS BIOLOGY,2018,16(11):28.
APA	Chen, Jianfeng.,Guo, Jun.,Zhang, Youhua.,Li, Hua.,Chu, Huiying.,...&Xu, Chenqi.(2018).Intramembrane ionic protein-lipid interaction regulates integrin structure and function.PLOS BIOLOGY,16(11),28.
MLA	Chen, Jianfeng,et al."Intramembrane ionic protein-lipid interaction regulates integrin structure and function".PLOS BIOLOGY 16.11(2018):28.