Completing the family portrait of the anti-apoptotic Bcl-2 proteins: Crystal structure of human Bfl-1 in complex with Bim

被引：65

作者：

Herman, Maria Dolores ^{[2
,3
]}

Nyman, Tomas ^{[1
]}

Welin, Martin ^{[1
]}

Lehtio, Lari ^{[1
]}

Flodin, Susanne ^{[1
]}

Tresaugues, Lionel ^{[1
]}

Kotenyova, Tetyana ^{[1
]}

Flores, Alex ^{[1
]}

Nordlund, Par ^{[1
,2
]}

机构：

[1] Karolinska Inst, Dept Med Biochem & Biophys, Struct Genom Consortium, S-17177 Stockholm, Sweden

[2] Karolinska Inst, Dept Med Biochem & Biophys, Div Biophys, S-17177 Stockholm, Sweden

[3] Stockholm Univ, Dept Biochem & Biophys, S-10691 Stockholm, Sweden

来源：

FEBS LETTERS | 2008年 / 582卷 / 25-26期

基金：

英国惠康基金; 英国医学研究理事会; 瑞典研究理事会;

关键词：

Apoptosis; B-cell lymphoma-2; Cancer; Bfl-1; A1; Crystal structure;

D O I：

10.1016/j.febslet.2008.09.028

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Evasion of apoptosis is recognized as a characteristic of malignant growth. Anti-apoptotic B-cell lymphoma-2 (Bcl-2) family members have therefore emerged as potential therapeutic targets due to their critical role in proliferating cancer cells. Here, we present the crystal structure of Bfl-1, the last antiapoptotic Bcl-2 family member to be structurally characterized, in complex with a peptide corresponding to the BH3 region of the pro-apoptotic protein Bim. The structure reveals distinct features at the peptide-binding site, likely to de. ne the binding pecificity for pro-apoptotic proteins. Superposition of the Bfl-1: Bim complex with that of Mcl-1: Bim reveals a significant local plasticity of hydrophobic interactions contributed by the Bim peptide, likely to be the basis for the multi specificity of Bim for antiapoptotic proteins. (c) 2008 Published by Elsevier B. V. on behalf of the Federation of European Biochemical Societies.

引用

页码：3590 / 3594

页数：5

共 31 条

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