Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
권호 표지
DOI QR코드

DOI QR Code

Oligomer Model of PB1 Domain of p62/SQSTM1 Based on Crystal Structure of Homo-Dimer and Calculation of Helical Characteristics

  • Lim, Dahwan (Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Lee, Hye Seon (Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Ku, Bonsu (Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Shin, Ho-Chul (Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Kim, Seung Jun (Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology)
  • Received : 2019.05.13
  • Accepted : 2019.09.04
  • Published : 2019.10.31
Download PDF
⟨ Previous Next ⟩

Abstract

Autophagy is an important process for protein recycling. Oligomerization of p62/SQSTM1 is an essential step in this process and is achieved in two steps. Phox and Bem1p (PB1) domains can oligomerize through both basic and acidic surfaces in each molecule. The ZZ-type zinc finger (ZZ) domain binds to target proteins and promotes higher-oligomerization of p62. This mechanism is an important step in routing target proteins to the autophagosome. Here, we determined the crystal structure of the PB1 homo-dimer and modeled the p62 PB1 oligomers. These oligomer models were represented by a cylindrical helix and were compared with the previously determined electron microscopic map of a PB1 oligomer. To accurately compare, we mathematically calculated the lead length and radius of the helical oligomers. Our PB1 oligomer model fits the electron microscopy map and is both bendable and stretchable as a flexible helical filament.

Keywords

References

  1. Adams, P.D., Afonine, P.V., Bunkoczi, G., Chen, V.B., Davis, I.W., Echols, N., Headd, J.J., Hung, L.W., Kapral, G.J., Grosse-Kunstleve, R.W., et al. (2010). PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D Biol. Crystallogr. 66, 213-221. https://doi.org/10.1107/S0907444909052925
  2. Bitto, A., Lerner, C.A., Nacarelli, T., Crowe, E., Torres, C., and Sell, C. (2014). P62/SQSTM1 at the interface of aging, autophagy, and disease. Age (Dordr) 36, 9626. https://doi.org/10.1007/s11357-014-9626-3
  3. Cha-Molstad, H., Sung, K.S., Hwang, J., Kim, K.A., Yu, J.E., Yoo, Y.D., Jang, J.M., Han, D.H., Molstad, M., Kim, J.G., et al. (2015). Amino-terminal arginylation targets endoplasmic reticulum chaperone BiP for autophagy through p62 binding. Nat. Cell Biol. 17, 917-929. https://doi.org/10.1038/ncb3177
  4. Ciuffa, R., Lamark, T., Tarafder, A.K., Guesdon, A., Rybina, S., Hagen, W.J., Johansen, T., and Sachse, C. (2015). The selective autophagy receptor p62 forms a flexible filamentous helical scaffold. Cell Rep. 11, 748-758. https://doi.org/10.1016/j.celrep.2015.03.062
  5. Emsley, P., Lohkamp, B., Scott, W.G., and Cowtan, K. (2010). Features and development of Coot. Acta Crystallogr. D Biol. Crystallogr. 66, 486-501. https://doi.org/10.1107/S0907444910007493
  6. Hirano, Y., Yoshinaga, S., Takeya, R., Suzuki, N.N., Horiuchi, M., Kohjima, M., Sumimoto, H., and Inagaki, F. (2005). Structure of a cell polarity regulator, a complex between atypical PKC and Par6 PB1 domains. J. Biol. Chem. 280, 9653-9661. https://doi.org/10.1074/jbc.M409823200
  7. Johansen, T. and Lamark, T. (2011). Selective autophagy mediated by autophagic adapter proteins. Autophagy 7, 279-296. https://doi.org/10.4161/auto.7.3.14487
  8. Katsuragi, Y., Ichimura, Y., and Komatsu, M. (2015). p62/SQSTM1 functions as a signaling hub and an autophagy adaptor. FEBS J. 282, 4672-4678. https://doi.org/10.1111/febs.13540
  9. Klionsky, D.J. and Emr, S.D. (2000). Autophagy as a regulated pathway of cellular degradation. Science 290, 1717-1721. https://doi.org/10.1126/science.290.5497.1717
  10. Knaevelsrud, H. and Simonsen, A. (2010). Fighting disease by selective autophagy of aggregate-prone proteins. FEBS Lett. 584, 2635-2645. https://doi.org/10.1016/j.febslet.2010.04.041
  11. Krissinel, E. and Henrick, K. (2007). Inference of macromolecular assemblies from crystalline state. J. Mol. Biol. 372, 774-797. https://doi.org/10.1016/j.jmb.2007.05.022
  12. Kwon, D.H., Park, O.H., Kim, L., Jung, Y.O., Park, Y., Jeong, H., Hyun, J., Kim, Y.K., and Song, H.K. (2018). Insights into degradation mechanism of N-end rule substrates by p62/SQSTM1 autophagy adapter. Nat. Commun. 9, 3291. https://doi.org/10.1038/s41467-018-05825-x
  13. Lamark, T., Perander, M., Outzen, H., Kristiansen, K., Overvatn, A., Michaelsen, E., Bjorkoy, G., and Johansen, T. (2003). Interaction codes within the family of mammalian Phox and Bem1p domain-containing proteins. J. Biol. Chem. 278, 34568-34581. https://doi.org/10.1074/jbc.M303221200
  14. Lin, X., Li, S., Zhao, Y., Ma, X., Zhang, K., He, X., and Wang, Z. (2013). Interaction domains of p62: a bridge between p62 and selective autophagy. DNA Cell Biol. 32, 220-227. https://doi.org/10.1089/dna.2012.1915
  15. Lippai, M. and Low, P. (2014). The role of the selective adaptor p62 and ubiquitin-like proteins in autophagy. Biomed. Res. Int. 2014, 832704.
  16. Minor, W., Cymborowski, M., Otwinowski, Z., and Chruszcz, M. (2006). HKL-3000: the integration of data reduction and structure solution--from diffraction images to an initial model in minutes. Acta Crystallogr. D Biol. Crystallogr. 62, 859-866. https://doi.org/10.1107/S0907444906019949
  17. Nakatogawa, H., Suzuki, K., Kamada, Y., and Ohsumi, Y. (2009). Dynamics and diversity in autophagy mechanisms: lessons from yeast. Nat. Rev. Mol. Cell Biol. 10, 458-467. https://doi.org/10.1038/nrm2708
  18. Nam, T., Han, J.H., Devkota, S., and Lee, H.W. (2017). Emerging paradigm of crosstalk between autophagy and the ubiquitin-proteasome system. Mol. Cells 40, 897-905. https://doi.org/10.14348/MOLCELLS.2017.0226
  19. Pettersen, E.F., Goddard, T.D., Huang, C.C., Couch, G.S., Greenblatt, D.M., Meng, E.C., and Ferrin, T.E. (2004). UCSF Chimera--a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605-1612. https://doi.org/10.1002/jcc.20084
  20. Ren, J., Wang, J., Wang, Z., and Wu, J. (2014). Structural and biochemical insights into the homotypic PB1-PB1 complex between PKCzeta and p62. Sci. China Life Sci. 57, 69-80. https://doi.org/10.1007/s11427-013-4592-z
  21. Rogov, V., Dotsch, V., Johansen, T., and Kirkin, V. (2014). Interactions between autophagy receptors and ubiquitin-like proteins form the molecular basis for selective autophagy. Mol. Cell 53, 167-178. https://doi.org/10.1016/j.molcel.2013.12.014
  22. Saio, T., Yokochi, M., and Inagaki, F. (2009). The NMR structure of the p62 PB1 domain, a key protein in autophagy and NF-kappaB signaling pathway. J. Biomol. NMR 45, 335-341. https://doi.org/10.1007/s10858-009-9370-7
  23. Saio, T., Yokochi, M., Kumeta, H., and Inagaki, F. (2010). PCS-based structure determination of protein-protein complexes. J. Biomol. NMR 46, 271-280. https://doi.org/10.1007/s10858-010-9401-4
  24. Schrodinger (2010). The PyMOL Molecular Graphics System, version 1.3r1 (New York: Schrodinger).
  25. Shin, H.C., Lim, D., Ku, B., and Kim, S.J. (2018). Purification, crystallization, and preliminary X-ray diffraction data analysis for PB1 dimer of P62/SQSTM1. Biodesign 6, 100-102.
  26. Varshavsky, A. (2017). The ubiquitin system, autophagy, and regulated protein degradation. Annu. Rev. Biochem. 86, 123-128. https://doi.org/10.1146/annurev-biochem-061516-044859
  27. Zhang, Y., Mun, S.R., Linares, J.F., Ahn, J., Towers, C.G., Ji, C.H., Fitzwalter, B.E., Holden, M.R., Mi, W., Shi, X., et al. (2018). ZZ-dependent regulation of p62/SQSTM1 in autophagy. Nat. Commun. 9, 4373. https://doi.org/10.1038/s41467-018-06878-8

Cited by

  1. Sequestsome-1/p62-targeted small molecules for pancreatic cancer therapy vol.27, pp.1, 2022, https://doi.org/10.1016/j.drudis.2021.09.011