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5juy

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Revision as of 18:44, 6 March 2020

Active human apoptosome with procaspase-9

5juy, resolution 4.10Å

Structural highlights

5juy is a 18 chain structure with sequence from Bos taurus and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	APAF1, KIAA0413 (HUMAN), CASP9, MCH6 (HUMAN)
Activity:	Caspase-9, with EC number 3.4.22.62
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[APAF_HUMAN] Oligomeric Apaf-1 mediates the cytochrome c-dependent autocatalytic activation of pro-caspase-9 (Apaf-3), leading to the activation of caspase-3 and apoptosis. This activation requires ATP. Isoform 6 is less effective in inducing apoptosis.^[1] ^[2] [CASP9_HUMAN] Involved in the activation cascade of caspases responsible for apoptosis execution. Binding of caspase-9 to Apaf-1 leads to activation of the protease which then cleaves and activates caspase-3. Promotes DNA damage-induced apoptosis in a ABL1/c-Abl-dependent manner. Proteolytically cleaves poly(ADP-ribose) polymerase (PARP).^[3] Isoform 2 lacks activity is an dominant-negative inhibitor of caspase-9.^[4] [CYC_BOVIN] Electron carrier protein. The oxidized form of the cytochrome c heme group can accept an electron from the heme group of the cytochrome c1 subunit of cytochrome reductase. Cytochrome c then transfers this electron to the cytochrome oxidase complex, the final protein carrier in the mitochondrial electron-transport chain. Plays a role in apoptosis. Suppression of the anti-apoptotic members or activation of the pro-apoptotic members of the Bcl-2 family leads to altered mitochondrial membrane permeability resulting in release of cytochrome c into the cytosol. Binding of cytochrome c to Apaf-1 triggers the activation of caspase-9, which then accelerates apoptosis by activating other caspases (By similarity).

Publication Abstract from PubMed

In response to cell death signals, an active apoptosome is assembled from Apaf-1 and procaspase-9 (pc-9). Here we report a near atomic structure of the active human apoptosome determined by cryo-electron microscopy. The resulting model gives insights into cytochrome c binding, nucleotide exchange and conformational changes that drive assembly. During activation an acentric disk is formed on the central hub of the apoptosome. This disk contains four Apaf-1/pc-9 CARD pairs arranged in a shallow spiral with the fourth pc-9 CARD at lower occupancy. On average, Apaf-1 CARDs recruit 3 to 5 pc-9 molecules to the apoptosome and one catalytic domain may be parked on the hub, when an odd number of zymogens are bound. This suggests a stoichiometry of one or at most, two pc-9 dimers per active apoptosome. Thus, our structure provides a molecular framework to understand the role of the apoptosome in programmed cell death and disease.

A near atomic structure of the active human apoptosome.,Cheng TC, Hong C, Akey IV, Yuan S, Akey CW Elife. 2016 Oct 4;5. pii: e17755. doi: 10.7554/eLife.17755. PMID:27697150^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Hu Y, Benedict MA, Ding L, Nunez G. Role of cytochrome c and dATP/ATP hydrolysis in Apaf-1-mediated caspase-9 activation and apoptosis. EMBO J. 1999 Jul 1;18(13):3586-95. PMID:10393175 doi:10.1093/emboj/18.13.3586
↑ Ogawa T, Shiga K, Hashimoto S, Kobayashi T, Horii A, Furukawa T. APAF-1-ALT, a novel alternative splicing form of APAF-1, potentially causes impeded ability of undergoing DNA damage-induced apoptosis in the LNCaP human prostate cancer cell line. Biochem Biophys Res Commun. 2003 Jun 27;306(2):537-43. PMID:12804598
↑ Raina D, Pandey P, Ahmad R, Bharti A, Ren J, Kharbanda S, Weichselbaum R, Kufe D. c-Abl tyrosine kinase regulates caspase-9 autocleavage in the apoptotic response to DNA damage. J Biol Chem. 2005 Mar 25;280(12):11147-51. Epub 2005 Jan 18. PMID:15657060 doi:10.1074/jbc.M413787200
↑ Raina D, Pandey P, Ahmad R, Bharti A, Ren J, Kharbanda S, Weichselbaum R, Kufe D. c-Abl tyrosine kinase regulates caspase-9 autocleavage in the apoptotic response to DNA damage. J Biol Chem. 2005 Mar 25;280(12):11147-51. Epub 2005 Jan 18. PMID:15657060 doi:10.1074/jbc.M413787200
↑ Cheng TC, Hong C, Akey IV, Yuan S, Akey CW. A near atomic structure of the active human apoptosome. Elife. 2016 Oct 4;5. pii: e17755. doi: 10.7554/eLife.17755. PMID:27697150 doi:http://dx.doi.org/10.7554/eLife.17755

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5juy"

@@ Line 1: / Line 1: @@
 ==Active human apoptosome with procaspase-9==
-<StructureSection load='5juy' size='340' side='right'caption='[[5juy]], [[Resolution|resolution]] 4.10&Aring;' scene=''>
+<SX load='5juy' size='340' side='right' viewer='molstar' caption='[[5juy]], [[Resolution|resolution]] 4.10&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[5juy]] is a 18 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JUY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5JUY FirstGlance]. <br>
@@ Line 29: / Line 29: @@
 <references/>
 __TOC__
-</StructureSection>
+</SX>
 [[Category: Bos taurus]]
 [[Category: Caspase-9]]

5juy

From Proteopedia

Revision as of 18:44, 6 March 2020

Active human apoptosome with procaspase-9

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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