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1z6t
From Proteopedia
| 1z6t, resolution 2.21Å () | |||||||||
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| Ligands: | |||||||||
| Domains: | CARD, NB-ARC | ||||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
Structure of the apoptotic protease-activating factor 1 bound to ADP
Apoptosis is executed by caspases, which undergo proteolytic activation in response to cell death stimuli. The apoptotic protease-activating factor 1 (Apaf-1) controls caspase activation downstream of mitochondria. During apoptosis, Apaf-1 binds to cytochrome c and in the presence of ATP/dATP forms an apoptosome, leading to the recruitment and activation of the initiator caspase, caspase-9 (ref. 2). The mechanisms underlying Apaf-1 function are largely unknown. Here we report the 2.2-A crystal structure of an ADP-bound, WD40-deleted Apaf-1, which reveals the molecular mechanism by which Apaf-1 exists in an inactive state before ATP binding. The amino-terminal caspase recruitment domain packs against a three-layered alpha/beta fold, a short helical motif and a winged-helix domain, resulting in the burial of the caspase-9-binding interface. The deeply buried ADP molecule serves as an organizing centre to strengthen interactions between these four adjoining domains, thus locking Apaf-1 in an inactive conformation. Apaf-1 binds to and hydrolyses ATP/dATP and their analogues. The binding and hydrolysis of nucleotides seem to drive conformational changes that are essential for the formation of the apoptosome and the activation of caspase-9.
Structure of the apoptotic protease-activating factor 1 bound to ADP., Riedl SJ, Li W, Chao Y, Schwarzenbacher R, Shi Y, Nature. 2005 Apr 14;434(7035):926-33. PMID:15829969
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
1Z6T is a 4 chains structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
- Riedl SJ, Li W, Chao Y, Schwarzenbacher R, Shi Y. Structure of the apoptotic protease-activating factor 1 bound to ADP. Nature. 2005 Apr 14;434(7035):926-33. PMID:15829969 doi:10.1038/nature03465
Page seeded by OCA on Mon Feb 16 16:18:47 2009
Categories: Homo sapiens | Chao, Y. | Li, W. | Riedl, S J. | Schwarzenbacher, R. | Shi, Y. | Adp | Apaf-1 | Card | Caspase activation | Nucleotide binding
