Apaf-1 and cytochrome c coassemble in the presence of dATP to form the apoptosome. We have determined a structure of the apoptosome at 12.8 A resolution by using electron cryomicroscopy and single-particle methods. We then docked appropriate crystal structures into the map to create an accurate domain model. Thus, we found that seven caspase recruitment domains (CARDs) form a central ring within the apoptosome. At a larger radius, seven copies of the nucleotide binding and oligomerization domain (NOD) associate laterally to form the hub, which encircles the CARD ring. Finally, an arm-like helical domain (HD2) links each NOD to a pair of beta propellers, which bind a single cytochrome c. This model provides insights into the roles of dATP and cytochrome c in assembly. Our structure also reveals how a CARD ring and the central hub combine to create a platform for procaspase-9 activation.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.str.2005.09.006 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Cell death regulation during influenza A virus infection by matrix (M1) protein: a model of viral control over the cellular survival pathway.
Cell Death Dis
September 2011
Division of Virology, National Institute of Cholera and Enteric Diseases, Beliaghata, Kolkata, India.
During early infection, viruses activate cellular stress-response proteins such as heat-shock proteins (Hsps) to counteract apoptosis, but later on, they modulate these proteins to stimulate apoptosis for efficient viral dissemination. Hsp70 has been attributed to modulate viral entry, transcription, nuclear translocation and virion formation. It also exerts its anti-apoptotic function by binding to apoptosis protease-activating factor 1 (Apaf-1) and disrupting apoptosome formation.
View Article and Find Full Text PDFStructure of the Drosophila apoptosome at 6.9 å resolution.
Structure
January 2011
Department of Physiology and Biophysics, Boston University School of Medicine, 700 Albany Street, Boston, MA 02118, USA.
The Drosophila Apaf-1 related killer forms an apoptosome in the intrinsic cell death pathway. In this study we show that Dark forms a single ring when initiator procaspases are bound. This Dark-Dronc complex cleaves DrICE efficiently; hence, a single ring represents the Drosophila apoptosome.
View Article and Find Full Text PDFDown-regulation of apoptosis mediators by RNAi inhibits axotomy-induced retinal ganglion cell death in vivo.
Brain
March 2005
Department of Neurology, University of Göttingen, Faculty of Medicine, S2-Laboratory, Waldweg 33, 37073 Göttingen, Germany.
Transection of the optic nerve induces an apoptotic degeneration of retinal ganglion cells (RGC) in the rat retina. The immediate early gene c-Jun, the proapoptotic Bcl-2 family member Bax and the apoptosome constituent Apaf-1 have been shown previously to play major roles in the induction or execution of the apoptosis cascade. In this study we have designed and generated short interfering RNAs (siRNAs) against c-Jun, Bax and Apaf-1, which were injected into the optic nerve stump in order to inhibit axotomy-induced apoptosis.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!