ArticleProceedings of the National Academy of Sciences of the United States of America2014
Integrated strategy reveals the protein interface between cancer targets Bcl-2 and NAF-1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 62 citations in OpenAlex.
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- CISD2 Promotes Resistance to Sorafenib-Induced Ferroptosis by Regulating Autophagy in Hepatocellular Carcinoma.Frontiers in oncology · 2021Article
- Epistatic contributions promote the unification of incompatible models of neutral molecular evolution.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
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- Phylogenetic correlations can suffice to infer protein partners from sequences.PLoS computational biology · 2019Article
- Redox-dependent gating of VDAC by mitoNEET.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Cathepsin B defines leader cells during the collective invasion of salivary adenoid cystic carcinoma.International journal of oncology · 2019Article
- NEET Proteins: A New Link Between Iron Metabolism, Reactive Oxygen Species, and Cancer.Antioxidants & redox signaling · 2019Review
- The anti-apoptotic proteins NAF-1 and iASPP interact to drive apoptosis in cancer cells.Chemical science · 2019Article
- Inferring interaction partners from protein sequences using mutual information.PLoS computational biology · 2018Article
- The unique fold and lability of the [2Fe-2S] clusters of NEET proteins mediate their key functions in health and disease.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2018Review
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Authors and funding
15 authors at 6 institutions in 4 countries.
Funding
Abstract
Life requires orchestrated control of cell proliferation, cell maintenance, and cell death. Involved in these decisions are protein complexes that assimilate a variety of inputs that report on the status of the cell and lead to an output response. Among the proteins involved in this response are nutrient-deprivation autophagy factor-1 (NAF-1)- and Bcl-2. NAF-1 is a homodimeric member of the novel Fe-S protein NEET family, which binds two 2Fe-2S clusters. NAF-1 is an important partner for Bcl-2 at the endoplasmic reticulum to functionally antagonize Beclin 1-dependent autophagy [Chang NC, Nguyen M, Germain M, Shore GC (2010) EMBO J 29(3):606-618]. We used an integrated approach involving peptide array, deuterium exchange mass spectrometry (DXMS), and functional studies aided by the power of sufficient constraints from direct coupling analysis (DCA) to determine the dominant docked conformation of the NAF-1-Bcl-2 complex. NAF-1 binds to both the pro- and antiapoptotic regions (BH3 and BH4) of Bcl-2, as demonstrated by a nested protein fragment analysis in a peptide array and DXMS analysis. A combination of the solution studies together with a new application of DCA to the eukaryotic proteins NAF-1 and Bcl-2 provided sufficient constraints at amino acid resolution to predict the interaction surfaces and orientation of the protein-protein interactions involved in the docked structure. The specific integrated approach described in this paper provides the first structural information, to our knowledge, for future targeting of the NAF-1-Bcl-2 complex in the regulation of apoptosis/autophagy in cancer biology.
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