Structure assembly of Bcl-X-L through alpha 5-alpha 5 and alpha 6-alpha 6 interhelix interactions in lipid membranes
文献类型：期刊论文
| 作者 | Feng, Yu2; Liu, Dongxiang2 ; Shen, Xu2; Chen, Kaixian1; Jiang, Hualiang1
|
| 刊名 | BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
 |
| 出版日期 | 2009-11 |
| 卷号 | 1788期号:11页码:2389-2395 |
| 关键词 | Bcl-X-L Pore formation Chemical cross-linking Apoptosis Membrane protein |
| ISSN号 | 0005-2736 |
| DOI | 10.1016/j.bbamem.2009.09.006 |
| 文献子类 | Article |
| 英文摘要 | Lipid bilayer membrane is the main site where Bcl-X-L executes its anti-apoptotic function. Here we used site-directed mutagenesis and cysteine-directed cross-linking to trap the structure of Bcl-X-L upon membrane insertion. Cys151 on alpha 5-helix and Asn185 on alpha 6-helix of two neighboring Bcl-XL are found in close positions, respectively. The FRET based binding assay indicated that the BH3-peptide binding pocket in Bcl-X-L is disrupted after its membrane insertion. Co-immunoprecipitation experiments showed that the membrane-bound Bcl-X-L sequestered tBid by direct interaction at physiological pH. If Bcl-X-L behaves similarly at low pH as it does at physiological pH, the membrane-bound Bcl-X-L should bind to tBid through protein regions other than the BH3 domain of tBid and the hydrophobic pocket of Bcl-X-L. Previously, a crystallography study demonstrated that Bcl-X-L formed homodimers through domain swapping in water, where Cys151 and Asn185 of two monomeric subunits are far apart from each other and the BH3-peptide binding pocket is intact. Our results indicated that Bcl-X-L dimer trapped by cross-linking in lipids is distinct from the domain swapped dimer, suggesting that Bcl-X-L transits through a structural change from the water-soluble state to the membrane-bound state and there are multiple possibilities for structural reorganization of Bcl-X-L protein. (C) 2009 Elsevier B.V. All rights reserved. |
| WOS关键词 | ANTIAPOPTOTIC PROTEIN BCL-2 ; ION-CHANNEL ; BCL-X(L) FORMS ; PORE FORMATION ; CELL-DEATH ; BAX ; DOMAIN ; APOPTOSIS ; MITOCHONDRIA ; DISTINCT |
| 资助项目 | CAS Introducing Outstanding Oversea Scientists Project[00000000] ; NSFC Innovation Program for Research Group[Grant 20721003] ; CAS Knowledge Innovation Program[KSCX2-YW-R-18] ; Shanghai Institute of Materia Medica[00000000] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Biophysics |
| 语种 | 英语 |
| WOS记录号 | WOS:000271671700005 |
| 出版者 | ELSEVIER SCIENCE BV |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279089]  |
| 专题 | 药理学第三研究室 药物发现与设计中心 |
| 通讯作者 | Liu, Dongxiang |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Design & Discovery, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Mol Pharmacol, Shanghai 201203, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Feng, Yu,Liu, Dongxiang,Shen, Xu,et al. Structure assembly of Bcl-X-L through alpha 5-alpha 5 and alpha 6-alpha 6 interhelix interactions in lipid membranes[J]. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES,2009,1788(11):2389-2395. |
| APA | Feng, Yu,Liu, Dongxiang,Shen, Xu,Chen, Kaixian,&Jiang, Hualiang.(2009).Structure assembly of Bcl-X-L through alpha 5-alpha 5 and alpha 6-alpha 6 interhelix interactions in lipid membranes.BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES,1788(11),2389-2395. |
| MLA | Feng, Yu,et al."Structure assembly of Bcl-X-L through alpha 5-alpha 5 and alpha 6-alpha 6 interhelix interactions in lipid membranes".BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES 1788.11(2009):2389-2395. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。