Dynamics and architecture of the NRBF2-containing phosphatidylinositol 3-kinase complex I of autophagy
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Significance: Autophagy (self-eating) is an essential process for cellular self-renewal. It is initiated by the ULK1 (unc-51 like autophagy activating kinase 1) protein kinase complex and the class III phosphatidylinositol 3-kinase complex I (PI3KC3-C1) lipid kinase complex, and understanding the structures of these large complexes is central to understanding how autophagy is initiated. Here we show that the protein nuclear receptor binding factor 2 (NRBF2) is the fifth subunit of the active form of PI3KC3-C1 and the NRBF2-containing complex is 10-fold more active. NRBF2 binds at the base of the V-shaped PI3KC3 architecture and changes protein motions, which may explain the change in enzyme activity. NRBF2 converts PI3KC3-C1 into a dimer, which changes how we think about the role of PI3KC3 in vesicle tethering.
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NRBF2 positively regulates the production of PtdIns3P.
“NRBF2 positively regulates the production of PtdIns3P. 27,28”
From NRBF2 is involved in the autophagic degradation process of APP-CTFs in Alzheimer disease models (2017) · cites this paper as [27]
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Cites
Repertoires of Autophagy in the Pathogenesis of Ocular Diseases
Li, Y., Jiang, Q. L., Cao, G.-F., Yao, J., & Yan, B. (2015) · Cellular Physiology and Biochemistry · doi:10.1159/000373980 · Cited by 16,351 · see citing works
Cui, C., Cui, J., Jin, F., Cui, Y., Li, R., Jiang, X., Tian, Y., Wang, R. C., Jiang, P., & Gao, J. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000479571 · Cited by 5,214 · see citing works
Bcl-2 Antiapoptotic Proteins Inhibit Beclin 1-Dependent Autophagy
Pattingre, S., Tassa, A., Qu, X., Garuti, R., Liang, X. H., Mizushima, N., Packer, M., Schneider, M. D., & Levine, B. (2005) · Cell · doi:10.1016/j.cell.2005.07.002 · Cited by 3,536 · see citing works
The Role of Atg Proteins in Autophagosome Formation
Mizushima, N., Yoshimori, T., & Ohsumi, Y. (2011) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-092910-154005 · Cited by 2,978 · see citing works
EMAN2: An extensible image processing suite for electron microscopy
Tang, G., Peng, L., Baldwin, P. R., Mann, D. S., Jiang, W., Rees, I., & Ludtke, S. J. (2006) · Journal of Structural Biology · doi:10.1016/j.jsb.2006.05.009 · Cited by 2,914 · see citing works
The role of autophagy in neurodegenerative disease
Nixon, R. A. (2013) · Nature Medicine · doi:10.1038/nm.3232 · Cited by 2,059 · see citing works
Automated molecular microscopy: The new Leginon system
Suloway, C. J. M., Pulokas, J., Fellmann, D., Cheng, A., Guerra, F., Quispe, J. D., Stagg, S. M., Potter, C. S., & Carragher, B. O. (2005) · Journal of Structural Biology · doi:10.1016/j.jsb.2005.03.010 · Cited by 1,681 · see citing works
Accurate determination of local defocus and specimen tilt in electron microscopy
Mindell, J. A., & Grigorieff, N. (2003) · Journal of Structural Biology · doi:10.1016/s1047-8477(03)00069-8 · Cited by 1,414 · see citing works
Autophagy in malignant transformation and cancer progression
Galluzzi, L., Pietrocola, F., Bravo‐San Pedro, J. M., Amaravadi, R. K., Baehrecke, E. H., Cecconi, F., Codogno, P., Debnath, J., Gewirtz, D. A., Karantza, V., et al. (2015) · The EMBO Journal · doi:10.15252/embj.201490784 · Cited by 1,182 · see citing works
Beclin 1 Forms Two Distinct Phosphatidylinositol 3-Kinase Complexes with Mammalian Atg14 and UVRAG
Itakura, E., Kishi, C., Inoue, K., & Mizushima, N. (2008) · Molecular Biology of the Cell · doi:10.1091/mbc.e08-01-0080 · Cited by 1,176 · see citing works
Autophagic and tumour suppressor activity of a novel Beclin1-binding protein UVRAG
Liang, C., Feng, P., Ku, B., Dotan, I., Canaani, D., Oh, B., & Jung, J. U. (2006) · Nature Cell Biology · doi:10.1038/ncb1426 · Cited by 1,025 · see citing works
Zhong, Y., Wang, Q. J., Li, X., Yan, Y., Backer, J. M., Chait, B. T., Heintz, N., & Yue, Z. (2009) · Nature Cell Biology · doi:10.1038/ncb1854 · Cited by 1,005 · see citing works
Appion: An integrated, database-driven pipeline to facilitate EM image processing
Lander, G. C., Stagg, S. M., Voss, N. R., Cheng, A., Fellmann, D., Pulokas, J., Yoshioka, C., Irving, C., Mulder, A. M., Lau, P., et al. (2009) · Journal of Structural Biology · doi:10.1016/j.jsb.2009.01.002 · Cited by 836 · see citing works
Ubiquitination and selective autophagy
Shaid, S., Brandts, C. H., Serve, H., & Dikic, I. (2013) · Cell Death & Differentiation · doi:10.1038/cdd.2012.72 · Cited by 800 · see citing works
The mystery of BCL2 family: Bcl-2 proteins and apoptosis: an update
Siddiqui, W. A., Ahad, A., & Ahsan, H. (2015) · Archives of Toxicology · doi:10.1007/s00204-014-1448-7 · Cited by 689 · see citing works
ATG14 promotes membrane tethering and fusion of autophagosomes to endolysosomes
Diao, J., Liu, R., Rong, Y., Zhao, M., Zhang, J., Lai, Y., Zhou, Q., Wilz, L., Li, J., Vivona, S., et al. (2015) · Nature · doi:10.1038/nature14147 · Cited by 592 · see citing works
Crystal Structure of the Bcl-XL-Beclin 1 Peptide Complex
Oberstein, A., Jeffrey, P. D., & Shi, Y. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m700492200 · Cited by 567 · see citing works
Sun, Q., Fan, W., Chen, K., Ding, X., Chen, S., & Zhong, Q. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0810452105 · Cited by 502 · see citing works
Primary structure effects on peptide group hydrogen exchange
Molday, R. S., Englander, S. W., & Kallen, R. G. (1972) · Biochemistry · doi:10.1021/bi00752a003 · Cited by 472 · see citing works
Autophagy requires endoplasmic reticulum targeting of the PI3-kinase complex via Atg14L
Matsunaga, K., Morita, E., Saitoh, T., Akira, S., Ktistakis, N. T., Izumi, T., Noda, T., & Yoshimori, T. (2010) · Journal of Cell Biology · doi:10.1083/jcb.200911141 · Cited by 456 · see citing works
Wang, W., Whorton, M. R., & MacKinnon, R. (2014) · eLife · doi:10.7554/elife.03671 · Cited by 444 · see citing works
Autophagic Processes in Yeast: Mechanism, Machinery and Regulation
Reggiori, F., & Klionsky, D. J. (2013) · Genetics · doi:10.1534/genetics.112.149013 · Cited by 404 · see citing works
Autophagosome targeting and membrane curvature sensing by Barkor/Atg14(L)
Fan, W., Nassiri, A., & Zhong, Q. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1016472108 · Cited by 285 · see citing works
mTORC1 Phosphorylates UVRAG to Negatively Regulate Autophagosome and Endosome Maturation
Kim, Y. M., Jung, C. H., Seo, M., Kim, E. K., Park, J.-M., Bae, S. S., & Kim, D. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.11.013 · Cited by 272 · see citing works
Architecture of the Atg17 Complex as a Scaffold for Autophagosome Biogenesis
Ragusa, M. J., Stanley, R. E., & Hurley, J. H. (2012) · Cell · doi:10.1016/j.cell.2012.11.028 · Cited by 253 · see citing works
Self-citationRostislavleva, K., Soler, N., Ohashi, Y., Zhang, L., Pardon, E., Burke, J. E., Masson, G. R., Johnson, C. M., Steyaert, J., Ktistakis, N. T., et al. (2015) · Science · doi:10.1126/science.aac7365 · Cited by 246 · see citing works
FindEM—a fast, efficient program for automatic selection of particles from electron micrographs
Roseman, A. M. (2003) · Journal of Structural Biology · doi:10.1016/j.jsb.2003.11.007 · Cited by 210 · see citing works
Beclin orthologs: integrative hubs of cell signaling, membrane trafficking, and physiology
Levine, B., Liu, R., Dong, X., & Zhong, Q. (2015) · Trends in Cell Biology · doi:10.1016/j.tcb.2015.05.004 · Cited by 177 · see citing works
Architecture and dynamics of the autophagic phosphatidylinositol 3-kinase complex
Baskaran, S., Carlson, L. A., Stjepanović, G., Young, L. N., Kim, D. J., Grob, P., Stanley, R. E., Nogales, E., & Hurley, J. H. (2014) · eLife · doi:10.7554/elife.05115 · Cited by 175 · see citing works
Self-citationLu, J., He, L., Behrends, C., Araki, M., Araki, K., Jun Wang, Q., Catanzaro, J. M., Friedman, S. L., Zong, W.-X., Fiel, M. I., et al. (2014) · Nature Communications · doi:10.1038/ncomms4920 · Cited by 148 · see citing works
Pantazatos, D., Kim, J. S., Klock, H. E., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0307204101 · Cited by 145 · see citing works
Ogura, T., Iwasaki, K., & Sato, C. (2003) · Journal of Structural Biology · doi:10.1016/j.jsb.2003.08.005 · Cited by 141 · see citing works
Atg38 is required for autophagy-specific phosphatidylinositol 3-kinase complex integrity
Araki, Y., Ku, W.-C., Akioka, M., May, A. I., Hayashi, Y., Arisaka, F., Ishihama, Y., & Ohsumi, Y. (2013) · Journal of Cell Biology · doi:10.1083/jcb.201304123 · Cited by 119 · see citing works
NRBF2 regulates macroautophagy as a component of Vps34 Complex I
Cao, Y., Wang, Y., Abi Saab, W. F., Yang, F., Pessin, J. E., & Backer, J. M. (2014) · Biochemical Journal · doi:10.1042/bj20140515 · Cited by 84 · see citing works
Zhong, Y., Morris, D. H., Jin, L., Patel, M. S., Karunakaran, S. K., Fu, Y.-J., Matuszak, E. A., Weiss, H. L., Chait, B. T., & Wang, Q. J. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.561134 · Cited by 79 · see citing works
Hurley, J. H., & Yang, D. J. (2008) · Developmental Cell · doi:10.1016/j.devcel.2007.12.013 · Cited by 62 · see citing works
Self-citationKöfinger, J., Ragusa, M. J., Lee, I., Hummer, G., & Hurley, J. H. (2015) · Structure · doi:10.1016/j.str.2015.02.012 · Cited by 38 · see citing works
Self-citationStructure and Function of Vps15 in the Endosomal G Protein Signaling Pathway ,
Heenan, E. J., Vanhooke, J. L., Temple, B. R. S., Betts, L., Sondek, J., & Dohlman, H. G. (2009) · Biochemistry · doi:10.1021/bi900621w · Cited by 33 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Lander GC, et al. (2009) Image Processing. Access 166(1):95-102.
Cited by
Sorted by citations
Extracellular vesicles: lipids as key components of their biogenesis and functions
Record, M., Silvente-Poirot, S., Poirot, M., & Wakelam, M. O. (2018) · Journal of Lipid Research · doi:10.1194/jlr.e086173 · Cited by 328 · see citing works
Structural Basis for Regulation of Phosphoinositide Kinases and Their Involvement in Human Disease
Burke, J. E. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.08.005 · Cited by 276 · see citing works
Lachance, V., Wang, Q., Sweet, E., Choi, I., Cai, C.-Z., Zhuang, X.-X., Zhang, Y., Jiang, J. L., Blitzer, R. D., Bozdagi-Gunal, O., et al. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0342-4 · Cited by 96 · see citing works
Crosstalk between apoptosis and autophagy signaling pathways
(2020) · International Review of Cell and Molecular Biology · doi:10.1016/bs.ircmb.2020.01.003 · Cited by 92 · see citing works
MTORC1-mediated NRBF2 phosphorylation functions as a switch for the class III PtdIns3K and autophagy
Ma, X., Zhang, S., He, L., Rong, Y., Brier, L. W., Sun, Q., Liu, R., Fan, W., Chen, S., Yue, Z., et al. (2017) · Autophagy · doi:10.1080/15548627.2016.1269988 · Cited by 92 · see citing works
NRBF2 is involved in the autophagic degradation process of APP-CTFs in Alzheimer disease models
Yang, C., Cai, C.-Z., Song, J.-X., Tan, J.-Q., Durairajan, S. S. K., Iyaswamy, A., Wu, M.-Y., Chen, L.-L., Yue, Z., Li, M., et al. (2017) · Autophagy · doi:10.1080/15548627.2017.1379633 · Cited by 83 · see citing works
- Authors
- Young, L. N., Cho, K., Lawrence, R., Zoncu, R., & Hurley, J. H.
- Affiliations
- QB3 (US)
- Corresponding author
- Hurley, James H.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2016-07-06
- Volume
- 113
- Issue
- 29
- Pages
- 8224-8229
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4961193
- OpenAlex
- W2469694753
- Cited by
- 89
- References
- 38
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 6 · 2023: 5 · 2022: 5 · 2021: 21 · 2020: 10 · 2019: 8 · 2018: 11 · 2017: 6 · 2016: 3
- FWCI
- 8.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- HHS | NIH | National Institute of General Medical Sciences (R01GM111730)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- class III phosphatidylinositol 3-kinase, autophagy initiation, Vps34, VPS15, Beclin-1, ATG14, complex architecture, lipid kinase activity, homodimerization, protein-protein interaction
- MeSH terms
- Autophagy-Related Proteins, Beclin-1, Autophagy, Escherichia coli, Humans, Trans-Activators, Adaptor Proteins, Vesicular Transport, HEK293 Cells, Class III Phosphatidylinositol 3-Kinases
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