Structure of an Apoptosome-Procaspase-9 CARD Complex

被引：102

作者：

Yuan, Shujun ^{[1
]}

Yu, Xinchao ^{[1
]}

Topf, Maya ^{[2
]}

Ludtke, Steven J. ^{[3
]}

Wang, Xiaodong ^{[4
]}

Akey, Christopher W. ^{[1
]}

机构：

[1] Boston Univ, Sch Med, Dept Physiol & Biophys, Boston, MA 02118 USA

[2] Univ London, Inst Struct & Mol Biol, Sch Crystallog, Dept Biol Sci, London WC1E 7HX, England

[3] Baylor Coll Med, Natl Ctr Macromol Imaging, Verna & Marrs McLean Dept Biochem & Mol Biol, Houston, TX 77030 USA

[4] Natl Inst Biol Sci, Beijing 102206, Peoples R China

来源：

STRUCTURE | 2010年 / 18卷 / 05期

基金：

英国医学研究理事会; 美国国家卫生研究院;

关键词：

PROTEASE-ACTIVATING FACTOR-1; CYTOCHROME-C BINDING; CELL-DEATH; BLAU-SYNDROME; 3-DIMENSIONAL STRUCTURE; CASPASE-9; ACTIVATION; NUCLEOTIDE EXCHANGE; PROVIDES INSIGHTS; APAF-1; APOPTOSOME;

D O I：

10.1016/j.str.2010.04.001

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：

Apaf-1 coassembles with cytochrome c to form the apoptosome, which then binds and activates procaspase-9 (pc-9). We removed pc-9 catalytic domains from the holoapoptosome by site-directed thrombinolysis. A structure of the resulting apoptosome-pc-9 CARD complex was then determined at similar to 9.5 angstrom resolution. In our model, the central hub is constructed like other AAA+ protein rings but also contains novel features. At higher radius, the regulatory region of each Apaf-1 is comprised of tandem seven and eight blade beta-propellers with cytochrome c docked between them. Remarkably, Apaf-1 CARDs are disordered in the ground state. During activation, each Apaf-1 CARD interacts with a pc-9 CARD and these heterodimers form a flexibly tethered "disk" that sits above the central hub. When taken together, the data reveal conformational changes during Apaf-1 assembly that allow pc-9 activation. The model also provides a plausible explanation for the effects of NOD mutations that have been mapped onto the central hub.

引用

页码：571 / 583

页数：13

共 58 条

[1] Three-dimensional structure of the apoptosome: Implications for assembly, procaspase-9 binding, and activation [J].

Acehan, D ;

Jiang, XJ ;

Morgan, DG ;

Heuser, JE ;

Wang, XD ;

Akey, CW .

MOLECULAR CELL, 2002, 9 (02) :423-432

[2] Calcium blocks formation of apoptosome by preventing nucleotide exchange in Apaf-1 [J].

Bao, Qing ;

Lu, Wenyun ;

Rabinowitz, Joshua D. ;

Shi, Yigong .

MOLECULAR CELL, 2007, 25 (02) :181-192

[3] A unified model for apical caspase activation [J].

Boatright, KM ;

Renatus, M ;

Scott, FL ;

Sperandio, S ;

Shin, H ;

Pedersen, IM ;

Ricci, JE ;

Edris, WA ;

Sutherlin, DP ;

Green, DR ;

Salvesen, GS .

MOLECULAR CELL, 2003, 11 (02) :529-541

[4] Cell death: Critical control points [J].

Danial, NN ;

Korsmeyer, SJ .

CELL, 2004, 116 (02) :205-219

[5] Wheel of Life, Wheel of Death: A Mechanistic Insight into Signaling by STAND Proteins [J].

Danot, Olivier ;

Marquenet, Emlie ;

Vidal-Ingigliardi, Dominique ;

Richet, Evelyne .

STRUCTURE, 2009, 17 (02) :172-182

[6] Complete structure of p97/valosin-containing protein reveals communication between nucleotide domains [J].

DeLaBarre, B ;

Brunger, AT .

NATURE STRUCTURAL BIOLOGY, 2003, 10 (10) :856-863

[7] Modeling AAA+ ring complexes from monomeric structures [J].

Diemand, Alexander V. ;

Lupas, Andrei N. .

JOURNAL OF STRUCTURAL BIOLOGY, 2006, 156 (01) :230-243

[8] Physiological and pathological roles of Apaf1 and the apoptosome [J].

Ferraro, E ;

Corvaro, M ;

Cecconi, F .

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2003, 7 (01) :21-34

[9] Software extensions to UCSF Chimera for interactive visualization of large molecular assemblies [J].

Goddard, TD ;

Huang, CC ;

Ferrin, TE .

STRUCTURE, 2005, 13 (03) :473-482

[10] A matter of life and death [J].

Green, DR ;

Evan, GI .

CANCER CELL, 2002, 1 (01) :19-30

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