A BAK subdomain that binds mitochondrial lipids selectively and releases cytochrome C
文献类型：期刊论文
| 作者 | Dai, Haiming1,3,4,5; Peterson, Kevin L.1; Flatten, Karen S.1; Meng, X. Wei1,5; Venkatachalam, Annapoorna1; Correia, Cristina1,5; Ramirez-Alvarado, Marina2; Pang, Yuan-Ping5; Kaufmann, Scott H.1,5 |
| 刊名 | CELL DEATH AND DIFFERENTIATION
 |
| 出版日期 | 2022-11-14 |
| ISSN号 | 1350-9047 |
| DOI | 10.1038/s41418-022-01083-z |
| 通讯作者 | Dai, Haiming(Dai.Haiming@Mayo.edu) ; Kaufmann, Scott H.(Kaufmann.Scott@Mayo.edu) |
| 英文摘要 | How BAK and BAX induce mitochondrial outer membrane (MOM) permeabilization (MOMP) during apoptosis is incompletely understood. Here we have used molecular dynamics simulations, surface plasmon resonance, and assays for membrane permeabilization in vitro and in vivo to assess the structure and function of selected BAK subdomains and their derivatives. Results of these studies demonstrate that BAK helical regions alpha 5 and alpha 6 bind the MOM lipid cardiolipin. While individual peptides corresponding to these helical regions lack the full biological activity of BAK, tandem peptides corresponding to alpha 4-alpha 5, alpha 5-alpha 6, or alpha 6-alpha 7/8 can localize exogenous proteins to mitochondria, permeabilize liposomes composed of MOM lipids, and cause MOMP in the absence of the remainder of the BAK protein. Importantly, the ability of these tandem helices to induce MOMP under cell-free conditions is diminished by mutations that disrupt the U-shaped helix-turn-helix structure of the tandem peptides or decrease their lipid binding. Likewise, BAK-induced apoptosis in intact cells is diminished by CLS1 gene interruption, which decreases mitochondrial cardiolipin content, or by BAK mutations that disrupt the U-shaped tandem peptide structure or diminish lipid binding. Collectively, these results suggest that BAK structural rearrangements during apoptosis might mobilize helices involved in specific protein-lipid interactions that are critical for MOMP. |
| WOS关键词 | CARDIOLIPIN PROVIDES ; CELL-DEATH ; RAT-LIVER ; MEMBRANE ; ACTIVATION ; APOPTOSIS ; INSERTION ; CANCER ; MODEL ; BH3 |
| 资助项目 | National Cancer Institute[R01 CA166741] ; National Cancer Institute[R01 CA225996] ; National Cancer Institute[P30 CA015083] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Cell Biology |
| 语种 | 英语 |
| 出版者 | SPRINGERNATURE |
| WOS记录号 | WOS:000883226800002 |
| 资助机构 | National Cancer Institute |
| 源URL | [http://ir.hfcas.ac.cn:8080/handle/334002/130327]  |
| 专题 | 中国科学院合肥物质科学研究院 |
| 通讯作者 | Dai, Haiming; Kaufmann, Scott H. |
| 作者单位 | 1.Mayo Clin Rochester, Div Oncol Res, Rochester, MN 55905 USA 2.Mayo Clin Rochester, Dept Biochem & Mol Biol, Rochester, MN 55905 USA 3.Chinese Acad Sci, Hefei Canc Hosp, Hefei 230031, Peoples R China 4.Chinese Acad Sci, Inst Hlth & Med Technol, Anhui Prov Key Lab Med Phys & Technol, Hefei Inst Phys Sci, Hefei 230031, Peoples R China 5.Mayo Clin Rochester, Dept Mol Pharmacol & Expt Therapeut, Rochester, MN 55905 USA |
| 推荐引用方式 GB/T 7714 | Dai, Haiming,Peterson, Kevin L.,Flatten, Karen S.,et al. A BAK subdomain that binds mitochondrial lipids selectively and releases cytochrome C[J]. CELL DEATH AND DIFFERENTIATION,2022. |
| APA | Dai, Haiming.,Peterson, Kevin L..,Flatten, Karen S..,Meng, X. Wei.,Venkatachalam, Annapoorna.,...&Kaufmann, Scott H..(2022).A BAK subdomain that binds mitochondrial lipids selectively and releases cytochrome C.CELL DEATH AND DIFFERENTIATION. |
| MLA | Dai, Haiming,et al."A BAK subdomain that binds mitochondrial lipids selectively and releases cytochrome C".CELL DEATH AND DIFFERENTIATION (2022). |
入库方式： OAI收割
来源：合肥物质科学研究院
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。