DICP OpenIR
Intramembrane ionic protein-lipid interaction regulates integrin structure and function
Guo, Jun1; Zhang, Youhua2,3; Li, Hua1; Chu, Huiying4; Wang, Qinshu5; Jiang, Shutan1; Li, Yan4; Shen, Hongbin6; Li, Guohui4; Chen, Jianfeng2; Xu, Chenqi1,5
Corresponding AuthorLi, Guohui(ghli@dicp.ac.cn) ; Chen, Jianfeng(jfchen@sibcb.ac.cn) ; Xu, Chenqi(cqxu@sibcb.ac.cn)
Source PublicationPLOS BIOLOGY
2018-11-01
ISSN1545-7885
DOI10.1371/journal.pbio.2006525
Volume16Issue:11Pages:28
Funding ProjectCAS[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]
Funding OrganizationCAS ; 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
WOS SubjectBiochemistry & Molecular Biology ; Biology
WOS Research AreaBiochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics
WOS KeywordT-CELL-ACTIVATION ; PLASMA-MEMBRANE ; DYNAMICS ; BINDING ; LFA-1 ; ALPHA-IIB-BETA-3 ; LYMPHOCYTES ; PERFORMANCE ; SELECTIVITY ; SYNAPSE
AbstractProtein 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.
Language英语
Funding OrganizationCAS ; 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
WOS IDWOS:000452442600009
PublisherPUBLIC LIBRARY SCIENCE
Citation statistics
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/166169
Collection中国科学院大连化学物理研究所
Corresponding AuthorLi, Guohui; Chen, Jianfeng; Xu, Chenqi
Affiliation1.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
2.Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci, Shanghai Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai, Peoples R China
3.Tongji Univ, Shanghai Peoples Hosp 10, Dept Pathol, Sch Med, 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
Recommended Citation
GB/T 7714
Guo, Jun,Zhang, Youhua,Li, Hua,et al. Intramembrane ionic protein-lipid interaction regulates integrin structure and function[J]. PLOS BIOLOGY,2018,16(11):28.
APA Guo, Jun.,Zhang, Youhua.,Li, Hua.,Chu, Huiying.,Wang, Qinshu.,...&Xu, Chenqi.(2018).Intramembrane ionic protein-lipid interaction regulates integrin structure and function.PLOS BIOLOGY,16(11),28.
MLA Guo, Jun,et al."Intramembrane ionic protein-lipid interaction regulates integrin structure and function".PLOS BIOLOGY 16.11(2018):28.
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