Apoptotic protease-activating factor

Function

Apoptosis protease-activating factor-1 (APAF-1) binds to cytochrome c and ATP to form the apoptosome which leads to the recruitment and activation of caspase 9 by cleaving the procaspase 9. Caspase 9 is involved in executing the apoptosis of cells^[1].

Disease

Inactivation of Apaf-1 is implicated in disease progression and chemoresistance of some malignancies^[2].

Structural highlights

Apaf-1 contains several copies of the WD-40 domain which are involved in binding to cytochrome c^[3]., caspase recruitment domain (CARD) and an ATPase domain.

formed by Human apoptosis protease-activating factor-1 (green; subunits A, B, C, D, E, F, G) complex with cytochrome c (red; H, I, J, K, L, M, N) and caspase 9 (magenta; O, P, Q, R) (PDB entry 5juy).

Human apoptosis protease-activating factor-1 (green) complex with cytochrome c (red) and caspase 9 (magenta) forming the apoptosome (PDB entry 5juy)

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3D structures of apoptosis protease-activating factor-13D structures of apoptosis protease-activating factor-1

Updated on 04-March-2018

2ygs, 1cy5, 2p1h – hAPAF-1 CARD domain – human
1c15, 1cww – hAPAF-1 CARD domain – NMR
1z6t – hAPAF-1 + ADP
3ygs – hAPAF-1 CARD domain + procaspase 9
4rhw, 5wvc – hAPAF-1 CARD domain + caspase 9
3j2t, 3jbt – hAPAF-1 + cytochrome c
5juy, 5wve – hAPAF-1 + caspase 9 + cytochrome c

ReferencesReferences

↑ 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
↑ Furukawa Y, Sutheesophon K, Wada T, Nishimura M, Saito Y, Ishii H, Furukawa Y. Methylation silencing of the Apaf-1 gene in acute leukemia. Mol Cancer Res. 2005 Jun;3(6):325-34. PMID:15972851 doi:http://dx.doi.org/10.1158/1541-7786.MCR-04-0105
↑ Shalaeva DN, Dibrova DV, Galperin MY, Mulkidjanian AY. Modeling of interaction between cytochrome c and the WD domains of Apaf-1: bifurcated salt bridges underlying apoptosome assembly. Biol Direct. 2015 May 27;10:29. doi: 10.1186/s13062-015-0059-4. PMID:26014357 doi:http://dx.doi.org/10.1186/s13062-015-0059-4

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Michal Harel, Joel L. Sussman, Alexander Berchansky

[1] 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

[2] Furukawa Y, Sutheesophon K, Wada T, Nishimura M, Saito Y, Ishii H, Furukawa Y. Methylation silencing of the Apaf-1 gene in acute leukemia. Mol Cancer Res. 2005 Jun;3(6):325-34. PMID:15972851 doi:http://dx.doi.org/10.1158/1541-7786.MCR-04-0105

[3] Shalaeva DN, Dibrova DV, Galperin MY, Mulkidjanian AY. Modeling of interaction between cytochrome c and the WD domains of Apaf-1: bifurcated salt bridges underlying apoptosome assembly. Biol Direct. 2015 May 27;10:29. doi: 10.1186/s13062-015-0059-4. PMID:26014357 doi:http://dx.doi.org/10.1186/s13062-015-0059-4

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