1z6t
From Proteopedia
(New page: 200px<br /> <applet load="1z6t" size="450" color="white" frame="true" align="right" spinBox="true" caption="1z6t, resolution 2.21Å" /> '''Structure of the ap...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1z6t.gif|left|200px]]<br /> | + | [[Image:1z6t.gif|left|200px]]<br /><applet load="1z6t" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1z6t" size=" | + | |
caption="1z6t, resolution 2.21Å" /> | caption="1z6t, resolution 2.21Å" /> | ||
'''Structure of the apoptotic protease-activating factor 1 bound to ADP'''<br /> | '''Structure of the apoptotic protease-activating factor 1 bound to ADP'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Apoptosis is executed by caspases, which undergo proteolytic activation in | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1Z6T is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ADP as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1Z6T is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ADP:'>ADP</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z6T OCA]. |
==Reference== | ==Reference== | ||
| Line 16: | Line 15: | ||
[[Category: Chao, Y.]] | [[Category: Chao, Y.]] | ||
[[Category: Li, W.]] | [[Category: Li, W.]] | ||
| - | [[Category: Riedl, S | + | [[Category: Riedl, S J.]] |
[[Category: Schwarzenbacher, R.]] | [[Category: Schwarzenbacher, R.]] | ||
[[Category: Shi, Y.]] | [[Category: Shi, Y.]] | ||
| Line 26: | Line 25: | ||
[[Category: nucleotide binding]] | [[Category: nucleotide binding]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:12:40 2008'' |
Revision as of 14:12, 21 February 2008
|
Structure of the apoptotic protease-activating factor 1 bound to ADP
Overview
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.
About this Structure
1Z6T is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Feb 21 16:12:40 2008
Categories: Homo sapiens | Single protein | Chao, Y. | Li, W. | Riedl, S J. | Schwarzenbacher, R. | Shi, Y. | ADP | Adp | Apaf-1 | Card | Caspase activation | Nucleotide binding
