A conserved hydrophobic core at Bcl-x(L) mediates its structural stability and binding affinity with BH3-domain peptide of pro-apoptotic protein

doi:10.1016/j.abb.2009.01.003

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第三研究室

	A conserved hydrophobic core at Bcl-x(L) mediates its structural stability and binding affinity with BH3-domain peptide of pro-apoptotic protein
	Feng, Yu 4; Zhang, Liang 4; Hu, Tianchen 4; Shen, Xu3,4 ; Ding, Jianping 1; Chen, Kaixian2 ; Jiang, Hualiang2,3 ; Liu, Dongxiang4
刊名	ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
	2009-04-01
卷号	484 期号:1 页码:46-54
关键词	Bcl-x(L) Hydrophobic core Protein stability Heterodimerization Pore formation
ISSN号	0003-9861
DOI	10.1016/j.abb.2009.01.003
文献子类	Article
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.
资助项目	CAS Introducing Outstanding Oversea Scientists Project[00000000] ; NSFC Innovation Program for Research Group[20721003] ; Shanghai Pu-Jiang Project[05PJ14110] ; CAS Knowledge Innovation Program[KSCX2-YW-R-18] ; Shanghai Institute of Materia Medica[00000000]
WOS关键词	BCL-2 FAMILY-MEMBERS ; X-RAY ; CELL-DEATH ; BAX ; MEMBRANES ; DISTINCT ; COMPLEX ; DOMAIN ; INHIBITION ; CHANNEL
WOS研究方向	Biochemistry & Molecular Biology ; Biophysics
语种	英语
出版者	ELSEVIER SCIENCE INC
WOS记录号	WOS:000264927700007
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279268]
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, Key Lab Prote, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China 2.Chinese Acad Sci, Ctr Drug Design & Discovery, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 3.E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China; 4.Chinese Acad Sci, Dept Mol Pharmacol, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China;
推荐引用方式 GB/T 7714	Feng, Yu,Zhang, Liang,Hu, Tianchen,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, Yu.,Zhang, Liang.,Hu, Tianchen.,Shen, Xu.,Ding, Jianping.,...&Liu, Dongxiang.(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, Yu,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.