Many players in BCL-2 family affairs

被引：498

作者：

Moldoveanu, Tudor ^{[1
]}

Follis, Ariele Viacava ^{[2
]}

Kriwacki, Richard W. ^{[2
]}

Green, Douglas R. ^{[1
]}

机构：

[1] St Jude Childrens Res Hosp, Dept Immunol, Memphis, TN 38105 USA

[2] St Jude Childrens Res Hosp, Dept Biol Struct, Memphis, TN 38105 USA

来源：

TRENDS IN BIOCHEMICAL SCIENCES | 2014年 / 39卷 / 03期

基金：

美国国家卫生研究院;

关键词：

B cell lymphoma-2 (BCL-2) family proteins; mitochondrial outer-membrane permeabilization (MOMP); mitochondrial apoptosis; EFFICIENTLY INDUCES APOPTOSIS; BH3-ONLY PROTEIN PUMA; BH3 MIMETIC ABT-199; DNA-BINDING DOMAIN; BAX ACTIVATION; CONFORMATIONAL-CHANGES; DEPENDENT APOPTOSIS; MEDIATED APOPTOSIS; STRUCTURAL BIOLOGY; OLIGOMERIZES BAK;

D O I：

10.1016/j.tibs.2013.12.006

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

During apoptotic cell death, cellular stress signals converge at the mitochondria to induce mitochondrial outer-membrane permeabilization (MOMP) through B cell lymphoma-2 (BCL-2) family proteins and their effectors. BCL-2 proteins function through protein-protein interactions, the mechanisms and structural aspects of which are only now being uncovered. Recently, the elucidation of the dynamic features underlying their function has highlighted their structural plasticity and the consequent complex thermodynamic landscape governing their protein-protein interactions. These studies show that canonical interactions involve a conserved, hydrophobic groove, whereas non-canonical interactions function allosterically outside the groove. We review the latest structural advances in understanding the interactions and functions of mammalian BCL-2 family members, and discuss new opportunities to modulate these proteins in health and disease.

引用

页码：101 / 111

页数：11

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