Structural highlights
Function
[BNIP3_HUMAN] Apoptosis-inducing protein that can overcome BCL2 suppression. May play a role in repartitioning calcium between the two major intracellular calcium stores in association with BCL2. Involved in mitochondrial quality control via its interaction with SPATA18/MIEAP: in response to mitochondrial damage, participates to mitochondrial protein catabolic process (also named MALM) leading to the degradation of damaged proteins inside mitochondria. The physical interaction of SPATA18/MIEAP, BNIP3 and BNIP3L/NIX at the mitochondrial outer membrane regulates the opening of a pore in the mitochondrial double membrane in order to mediate the translocation of lysosomal proteins from the cytoplasm to the mitochondrial matrix. Plays an important role in the calprotectin (S100A8/A9)-induced cell death pathway.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
BNip3 is a prominent representative of apoptotic Bcl-2 proteins with rather unique properties initiating an atypical programmed cell death pathway resembling both necrosis and apoptosis. Many Bcl-2 family proteins modulate the permeability state of the outer mitochondrial membrane by forming homo- and hetero-oligomers. The structure and dynamics of the homodimeric transmembrane domain of BNip3 were investigated with the aid of solution NMR in lipid bicelles and molecular dynamics energy relaxation in an explicit lipid bilayer. The right-handed parallel helix-helix structure of the domain with a hydrogen bond-rich His-Ser node in the middle of the membrane, accessibility of the node for water, and continuous hydrophilic track across the membrane suggest that the domain can provide an ion-conducting pathway through the membrane. Incorporation of the BNip3 transmembrane domain into an artificial lipid bilayer resulted in pH-dependent conductivity increase. A possible biological implication of the findings in relation to triggering necrosis-like cell death by BNip3 is discussed.
Unique dimeric structure of BNip3 transmembrane domain suggests membrane permeabilization as a cell death trigger.,Bocharov EV, Pustovalova YE, Pavlov KV, Volynsky PE, Goncharuk MV, Ermolyuk YS, Karpunin DV, Schulga AA, Kirpichnikov MP, Efremov RG, Maslennikov IV, Arseniev AS J Biol Chem. 2007 Jun 1;282(22):16256-66. Epub 2007 Apr 4. PMID:17412696[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ghavami S, Eshragi M, Ande SR, Chazin WJ, Klonisch T, Halayko AJ, McNeill KD, Hashemi M, Kerkhoff C, Los M. S100A8/A9 induces autophagy and apoptosis via ROS-mediated cross-talk between mitochondria and lysosomes that involves BNIP3. Cell Res. 2010 Mar;20(3):314-31. doi: 10.1038/cr.2009.129. Epub 2009 Nov 24. PMID:19935772 doi:10.1038/cr.2009.129
- ↑ Nakamura Y, Kitamura N, Shinogi D, Yoshida M, Goda O, Murai R, Kamino H, Arakawa H. BNIP3 and NIX mediate Mieap-induced accumulation of lysosomal proteins within mitochondria. PLoS One. 2012;7(1):e30767. doi: 10.1371/journal.pone.0030767. Epub 2012 Jan 26. PMID:22292033 doi:http://dx.doi.org/10.1371/journal.pone.0030767
- ↑ Bocharov EV, Pustovalova YE, Pavlov KV, Volynsky PE, Goncharuk MV, Ermolyuk YS, Karpunin DV, Schulga AA, Kirpichnikov MP, Efremov RG, Maslennikov IV, Arseniev AS. Unique dimeric structure of BNip3 transmembrane domain suggests membrane permeabilization as a cell death trigger. J Biol Chem. 2007 Jun 1;282(22):16256-66. Epub 2007 Apr 4. PMID:17412696 doi:10.1074/jbc.M701745200
