| Structural highlights
Function
[HEBP2_HUMAN] Can promote mitochondrial permeability transition and facilitate necrotic cell death under different types of stress conditions. Does not bind hemin.[1] [PDCD6_HUMAN] Calcium-binding protein required for T-cell receptor-, Fas-, and glucocorticoid-induced cell death. May mediate Ca(2+)-regulated signals along the death pathway (By similarity). Calcium-dependent adapter necessary for the association between PDCD6IP and TSG101. Interaction with DAPK1 can accelerate apoptotic cell death by increasing caspase-3 activity.[2] [3]
Publication Abstract from PubMed
In the HIV-1 replication cycle, the endosomal sorting complex required for transport (ESCRT) machinery promotes viral budding and release in the late stages. In this process, the ESCRT proteins, ALIX and TSG101, are recruited through interactions with HIV-1 Gag p6. ALG-2, also known as PDCD6, interacts with both ALIX and TSG101 and bridges ESCRT-III and ESCRT-I. In this study, we show that ALG-2 affects HIV-1 production negatively at both the exogenous and endogenous levels. Through a yeast two-hybrid screen, we identified HEBP2 as the binding partner of ALG-2, and we solved the crystal structure of the ALG-2.HEBP2 complex. The function of ALG-2.HEBP2 complex in HIV-1 replication was further explored. ALG-2 inhibits HIV-1 production by affecting Gag expression and distribution, and HEBP2 might aid this process by tethering ALG-2 in the cytoplasm.
Structural and Functional Study of Apoptosis-linked Gene-2.Heme-binding Protein 2 Interactions in HIV-1 Production.,Ma J, Zhang X, Feng Y, Zhang H, Wang X, Zheng Y, Qiao W, Liu X J Biol Chem. 2016 Dec 23;291(52):26670-26685. doi: 10.1074/jbc.M116.752444. Epub , 2016 Oct 26. PMID:27784779[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Szigeti A, Bellyei S, Gasz B, Boronkai A, Hocsak E, Minik O, Bognar Z, Varbiro G, Sumegi B, Gallyas F Jr. Induction of necrotic cell death and mitochondrial permeabilization by heme binding protein 2/SOUL. FEBS Lett. 2006 Nov 27;580(27):6447-54. Epub 2006 Nov 7. PMID:17098234 doi:http://dx.doi.org/10.1016/j.febslet.2006.10.067
- ↑ Lee JH, Rho SB, Chun T. Programmed cell death 6 (PDCD6) protein interacts with death-associated protein kinase 1 (DAPk1): additive effect on apoptosis via caspase-3 dependent pathway. Biotechnol Lett. 2005 Jul;27(14):1011-5. PMID:16132846 doi:http://dx.doi.org/10.1007/s10529-005-7869-x
- ↑ Okumura M, Ichioka F, Kobayashi R, Suzuki H, Yoshida H, Shibata H, Maki M. Penta-EF-hand protein ALG-2 functions as a Ca2+-dependent adaptor that bridges Alix and TSG101. Biochem Biophys Res Commun. 2009 Aug 14;386(1):237-41. doi:, 10.1016/j.bbrc.2009.06.015. Epub 2009 Jun 9. PMID:19520058 doi:http://dx.doi.org/10.1016/j.bbrc.2009.06.015
- ↑ Ma J, Zhang X, Feng Y, Zhang H, Wang X, Zheng Y, Qiao W, Liu X. Structural and Functional Study of Apoptosis-linked Gene-2.Heme-binding Protein 2 Interactions in HIV-1 Production. J Biol Chem. 2016 Dec 23;291(52):26670-26685. doi: 10.1074/jbc.M116.752444. Epub , 2016 Oct 26. PMID:27784779 doi:http://dx.doi.org/10.1074/jbc.M116.752444
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