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Characterization of an alternative BAK-binding site for BH3 peptides

文献类型：期刊论文

作者Ye, Kaiqin2,3; Meng, Wei X.4,5; Sun, Hongbin1; Wu, Bo6; Chen, Meng2,3; Pang, Yuan-Ping5; Gao, Jia2,3; Wang, Hongzhi2,3; Wang, Junfeng6; Kaufmann, Scott H.4,5
刊名NATURE COMMUNICATIONS
出版日期2020-07-03
卷号11
ISSN号2041-1723
DOI10.1038/s41467-020-17074-y
通讯作者Kaufmann, Scott H.(Kaufmann.Scott@mayo.edu) ; Dai, Haiming(daih@cmpt.ac.cn)
英文摘要Many cellular stresses are transduced into apoptotic signals through modification or up-regulation of the BH3-only subfamily of BCL2 proteins. Through direct or indirect mechanisms, these proteins activate BAK and BAX to permeabilize the mitochondrial outer membrane. While the BH3-only proteins BIM, PUMA, and tBID have been confirmed to directly activate BAK through its canonical BH3 binding groove, whether the BH3-only proteins BMF, HRK or BIK can directly activate BAK is less clear. Here we show that BMF and HRK bind and directly activate BAK. Through NMR studies, site-directed mutagenesis, and advanced molecular dynamics simulations, we also find that BAK activation by BMF and possibly HRK involves a previously unrecognized binding groove formed by BAK alpha 4, alpha 6, and alpha 7 helices. Alterations in this groove decrease the ability of BMF and HRK to bind BAK, permeabilize membranes and induce apoptosis, suggesting a potential role for this BH3-binding site in BAK activation. Mitochondrial apoptosis is controlled by BCL2 family proteins, and the BH3-only proteins often act as sensors that transmit apoptotic signals. Here the authors show how the BH3-only proteins BMF and HRK can directly activate the BCL2 protein BAK and interact with BAK through an alternative binding groove.
WOS关键词BH3-ONLY PROTEIN PUMA ; CONFORMATIONAL-CHANGES ; MEMBRANE INSERTION ; ACTIVATION ; APOPTOSIS ; DOMAINS ; BIM ; SENSITIVITY ; INTERFACE ; BMF
资助项目National Natural Science Foundation of China[81572948] ; National Natural Science Foundation of China[21772201] ; National Natural Science Foundation of China[21703254] ; Hundred-Talents Program of Chinese Academy of Science ; innovative program of Development Foundation of Hefei Center for Physical Science and Technology[2018CXFX007] ; Hefei Foreign Cooperation Project[ZR201801020002] ; President Foundation of Hefei Institutes of Physical Science of Chinese Academy of Sciences[YZJJ201623]
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:000546623500001
出版者NATURE PUBLISHING GROUP
资助机构National Natural Science Foundation of China ; Hundred-Talents Program of Chinese Academy of Science ; innovative program of Development Foundation of Hefei Center for Physical Science and Technology ; Hefei Foreign Cooperation Project ; President Foundation of Hefei Institutes of Physical Science of Chinese Academy of Sciences
源URL[http://ir.hfcas.ac.cn:8080/handle/334002/71203]  
专题中国科学院合肥物质科学研究院
通讯作者Kaufmann, Scott H.; Dai, Haiming
作者单位1.Zhenzhou Univ Light Ind, Sch Food & Biol Engn, Zhenzhou 450002, Peoples R China
2.Chinese Acad Sci, Hefei Inst Phys Sci, Ctr Med Phys & Technol, Anhui Prov Key Lab Med Phys & Technol, Hefei 230031, Peoples R China
3.Chinese Acad Sci, Hefei Canc Hosp, Hefei 230031, Peoples R China
4.Mayo Clin, Div Oncol Res, Rochester, MN 55905 USA
5.Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Rochester, MN 55905 USA
6.Chinese Acad Sci, HFIPS, High Field Magnet Lab, CAS Key Lab High Magnet Field & Ion Beam Phys Bio, Hefei 230031, Peoples R China
推荐引用方式
GB/T 7714		 Ye, Kaiqin,Meng, Wei X.,Sun, Hongbin,et al. Characterization of an alternative BAK-binding site for BH3 peptides[J]. NATURE COMMUNICATIONS,2020,11.
APA Ye, Kaiqin.,Meng, Wei X..,Sun, Hongbin.,Wu, Bo.,Chen, Meng.,...&Dai, Haiming.(2020).Characterization of an alternative BAK-binding site for BH3 peptides.NATURE COMMUNICATIONS,11.
MLA Ye, Kaiqin,et al."Characterization of an alternative BAK-binding site for BH3 peptides".NATURE COMMUNICATIONS 11(2020).

入库方式： OAI收割

来源：合肥物质科学研究院

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