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Impairment on the lateral mobility induced by structural changes underlies the functional deficiency of the lupus-associated polymorphism Fc gamma RIIB-T232 | |
Xu, Liling1; Xia, Mengdie2; Guo, Jun3; Sun, Xiaolin4; Li, Hua3; Xu, Chenguang1; Gu, Xiaomei1; Zhang, Haowen1; Yi, Junyang1; Fang, Yan1; Xie, Hengyi1; Wang, Jing1; Shen, Zhixun1; Xue, Boxin5; Sun, Yujie5; Meckel, Tobias6; Chen, Ying-Hua1; Hu, Zhibin7; Li, Zhanguo4; Xu, Chenqi3,8 ![]() | |
2016-11 | |
发表期刊 | JOURNAL OF EXPERIMENTAL MEDICINE
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ISSN | 0022-1007 |
卷号 | 213期号:12页码:2707-2727 |
发表状态 | 已发表 |
DOI | 10.1084/jem.20160528 |
摘要 | Fc gamma RIIB functions to suppress the activation of immune cells. A single-nucleotide polymorphism in the transmembrane (TM) domain of Fc gamma RIIB, Fc gamma RIIB-T232, is associated with lupus. In this study, we investigated the pathogenic mechanism of Fc gamma RIIB- T232 at both functional and structural levels. Our results showed that Fc gamma RIIB-T232 exhibited significantly reduced lateral mobility compared with Fc gamma RIIB-I232 and was significantly less enriched into the microclusters of immune complexes (ICs) after stimulation. However, if sufficient responding time is given for Fc gamma RIIB-T232 to diffuse and interact with the ICs, Fc gamma RIIB-T232 can restore its inhibitory function. Moreover, substituting the Fc gamma RIIB-T232 TM domain with that of a fast floating CD86 molecule restored both the rapid mobility and the inhibitory function, which further corroborated the importance of fast mobility for Fc gamma RIIB to function. Mechanistically, the crippled lateral mobility of Fc gamma RIIB-T232 can be explained by the structural changes of the TM domain. Both atomistic simulations and nuclear magnetic resonance measurement indicated that the TM helix of Fc gamma RIIB-T232 exhibited a more inclined orientation than that of Fc gamma RIIB-I232, thus resulting in a longer region embedded in the membrane. Therefore, we conclude that the single-residue polymorphism T232 enforces the inclination of the TM domain and thereby reduces the lateral mobility and inhibitory functions of Fc gamma RIIB. |
收录类别 | SCI |
语种 | 英语 |
资助项目 | MOST[2011CB910901] ; MOST[2012CB910804] ; MOST[2014CB541903] |
WOS研究方向 | Immunology ; Research & Experimental Medicine |
WOS类目 | Immunology ; Medicine, Research & Experimental |
WOS记录号 | WOS:000391122400013 |
出版者 | ROCKEFELLER UNIV PRESS |
WOS关键词 | FC-GAMMA-RIIB ; B-CELL-RECEPTOR ; SINGLE-MOLECULE TRACKING ; PLASMA-MEMBRANE ; LIPID RAFTS ; ERYTHEMATOSUS ; PROTEIN ; SUSCEPTIBILITY ; DYNAMICS ; NMR |
原始文献类型 | Article |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1652 |
专题 | 生命科学与技术学院_特聘教授组_许琛琦组 |
通讯作者 | Li, Zhanguo; Xu, Chenqi; Gong, Haipeng; Liu, Wanli |
作者单位 | 1.Tsinghua Univ, Minist Educ, Collaborat Innovat Ctr Diag & Treatment Infect Di, Key Lab Prot Sci,Inst Immunol, Beijing 100084, Peoples R China 2.Tsinghua Univ, Sch Life Sci, Key Lab Bioinformat, Minist Educ, Beijing 100084, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol,Natl Ctr Prot Sci Shanghai, Shanghai 200031, Peoples R China 4.Peking Univ, Dept Rheumatol & Immunol, Clin Immunol Ctr, Peoples Hosp, Beijing 100044, Peoples R China 5.Peking Univ, Sch Life Sci, Biodynam Opt Imaging Ctr, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100871, Peoples R China 6.Tech Univ Darmstadt, Dept Biol, Membrane Dynam, D-64287 Darmstadt, Germany 7.Nanjing Med Univ, Sch Publ Hlth, Dept Epidemiol, Nanjing 211166, Jiangsu, Peoples R China 8.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 200031, 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 | Xu, Liling,Xia, Mengdie,Guo, Jun,et al. Impairment on the lateral mobility induced by structural changes underlies the functional deficiency of the lupus-associated polymorphism Fc gamma RIIB-T232[J]. JOURNAL OF EXPERIMENTAL MEDICINE,2016,213(12):2707-2727. |
APA | Xu, Liling.,Xia, Mengdie.,Guo, Jun.,Sun, Xiaolin.,Li, Hua.,...&Liu, Wanli.(2016).Impairment on the lateral mobility induced by structural changes underlies the functional deficiency of the lupus-associated polymorphism Fc gamma RIIB-T232.JOURNAL OF EXPERIMENTAL MEDICINE,213(12),2707-2727. |
MLA | Xu, Liling,et al."Impairment on the lateral mobility induced by structural changes underlies the functional deficiency of the lupus-associated polymorphism Fc gamma RIIB-T232".JOURNAL OF EXPERIMENTAL MEDICINE 213.12(2016):2707-2727. |
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