Integration and Oligomerization of Bax Protein in Lipid Bilayers Characterized by Single Molecule Fluorescence Study
文献类型：期刊论文
| 作者 | Luo, Lu1,2; Yang, Jun3; Liu, Dongxiang1,2
|
| 刊名 | JOURNAL OF BIOLOGICAL CHEMISTRY
 |
| 出版日期 | 2014-11-14 |
| 卷号 | 289期号:46页码:31708-31718 |
| 关键词 | Apoptosis B-cell Lymphoma 2 (Bcl-2) Family Bax Lipid Bilayer Single Molecule Biophysics |
| ISSN号 | 0021-9258 |
| DOI | 10.1074/jbc.M114.583393 |
| 文献子类 | Article |
| 英文摘要 | Background: The stoichiometry of Bax oligomers on mitochondria and the process of Bax pore formation remain unclear. Results: Bax oligomerization occurs only if tBid is present, and its membrane insertion highly depends on cardiolipin; Bax tends to form tetramer on membrane. Conclusion: Bax pore formation involves two independent steps: Bax oligomerization and membrane insertion. Significance: This study may help elucidate Bax pore formation. Bax is a pro-apoptotic Bcl-2 family protein. The activated Bax translocates to mitochondria, where it forms pore and permeabilizes the mitochondrial outer membrane. This process requires the BH3-only activator protein (i.e. tBid) and can be inhibited by anti-apoptotic Bcl-2 family proteins such as Bcl-x(L). Here by using single molecule fluorescence techniques, we studied the integration and oligomerization of Bax in lipid bilayers. Our study revealed that Bax can bind to lipid membrane spontaneously in the absence of tBid. The Bax pore formation undergoes at least two steps: pre-pore formation and membrane insertion. The activated Bax triggered by tBid or BH3 domain peptide integrates on bilayers and tends to form tetramers, which are termed as pre-pore. Subsequent insertion of the pre-pore into membrane is highly dependent on the composition of cardiolipin in lipid bilayers. Bcl-x(L) can translocate Bax from membrane to solution and inhibit the pore formation. The study of Bax integration and oligomerization at the single molecule level provides new evidences that may help elucidate the pore formation of Bax and its regulatory mechanism in apoptosis. |
| WOS关键词 | OUTER MITOCHONDRIAL-MEMBRANE ; CYTOCHROME-C RELEASE ; CONFORMATIONAL-CHANGE ; BH3 DOMAINS ; CELL-DEATH ; APOPTOSIS ; ACTIVATION ; BCL-2 ; PERMEABILIZATION ; INSERTION |
| 资助项目 | National Science Fund[21472206] ; State Key Laboratory of Drug Research[00000000] |
| WOS研究方向 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000345314700005 |
| 出版者 | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276838]  |
| 专题 | 药理学第三研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Liu, Dongxiang |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Pharmacol 3, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 3.Shanghai Inst Planned Parenthood Res, Shanghai 200032, Peoples R China |
| 推荐引用方式 GB/T 7714 | Luo, Lu,Yang, Jun,Liu, Dongxiang. Integration and Oligomerization of Bax Protein in Lipid Bilayers Characterized by Single Molecule Fluorescence Study[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2014,289(46):31708-31718. |
| APA | Luo, Lu,Yang, Jun,&Liu, Dongxiang.(2014).Integration and Oligomerization of Bax Protein in Lipid Bilayers Characterized by Single Molecule Fluorescence Study.JOURNAL OF BIOLOGICAL CHEMISTRY,289(46),31708-31718. |
| MLA | Luo, Lu,et al."Integration and Oligomerization of Bax Protein in Lipid Bilayers Characterized by Single Molecule Fluorescence Study".JOURNAL OF BIOLOGICAL CHEMISTRY 289.46(2014):31708-31718. |
入库方式： OAI收割
来源：上海药物研究所
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