A conserved hydrophobic core at Bcl-x(L) mediates its structural stability and binding affinity with BH3-domain peptide of pro-apoptotic protein
文献类型：期刊论文
| 作者 | Feng, Y; Zhang, L; Hu, TC; Shen, X; Ding, JP; Chen, KX; Jiang, HL; Liu, DX |
| 刊名 | ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
 |
| 出版日期 | 2009 |
| 卷号 | 484期号:1页码:46-54 |
| 关键词 | Bcl-x(L) Hydrophobic core Protein stability Heterodimerization Pore formation |
| 通讯作者 | Liu, DX (reprint author), Chinese Acad Sci, Dept Mol Pharmacol, Shanghai Inst Mat Med, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China.,dxl@mail.shcnc.ac.cn |
| 英文摘要 | Bcl-2 family proteins regulate apoptosis through their homo- and heterodimerization. By protein sequence analysis and structural comparison, we have identified a conserved hydrophobic core at the BH1 and BH2 domains of Bcl-2 family proteins. The hydrophobic core is stabilized by hydrophobic interactions among the residues of Trp137, Ile140, Trp181, Ile182, Trp188 and Phe191 in Bcl-x(L). Destabilization of the hydrophobic core can promote the protein unforlding and pore formation in synthetic lipid vesicles. Interestingly, through the hydrophobic core does not participate in binding with BH3 domain of pro-apoptotic proteins, disruption of the hydrophobic core can reduce the affinity of Bcl-x(L) with BH3-domain peptide by changing the conformation of Bcl-x(L) C-terminal residues that are involved in the peptide interaction. The BH3-domain peptide binding affinity and pore forming propensity of Bcl-x(L) were correlated to its death-repressor activity, which provides new information to help study the regulatory mechanism of anti-apoptotic proteins. Meanwhile, as the tryptophans are conserved in the hydrophobic core, in vitro binding assay based on FRET of "Trp - AEDANS" can be devised to screen for new modulators targeting anti-apoptotic proteins as well as "multi-BH domains" pro-apoptotic proteins. (C) 2009 Elseiver Inc. All rights reserved. |
| 学科主题 | Biochemistry & Molecular Biology ; Biophysics |
| 类目[WOS] | Biochemistry & Molecular Biology ; Biophysics |
| 关键词[WOS] | BCL-2 FAMILY-MEMBERS ; X-RAY ; CELL-DEATH ; BAX ; MEMBRANES ; DISTINCT ; COMPLEX ; DOMAIN ; INHIBITION ; CHANNEL |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000264927700007 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/1120]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Feng, Y,Zhang, L,Hu, TC,et al. A conserved hydrophobic core at Bcl-x(L) mediates its structural stability and binding affinity with BH3-domain peptide of pro-apoptotic protein[J]. ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS,2009,484(1):46-54. |
| APA | Feng, Y.,Zhang, L.,Hu, TC.,Shen, X.,Ding, JP.,...&Liu, DX.(2009).A conserved hydrophobic core at Bcl-x(L) mediates its structural stability and binding affinity with BH3-domain peptide of pro-apoptotic protein.ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS,484(1),46-54. |
| MLA | Feng, Y,et al."A conserved hydrophobic core at Bcl-x(L) mediates its structural stability and binding affinity with BH3-domain peptide of pro-apoptotic protein".ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS 484.1(2009):46-54. |
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