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Targeted protein degradation

You can glue it too!

Proteolysis-targeting chimera (PROTACs) are synthetic molecules that recruit neo-substrate proteins to a ubiquitin ligase for ubiquitination and subsequent degradation. Structural insight into the VHL–MZ1–BRD4 complex reveals how the rationally designed MZ1–PROTAC molecule mediates degradation of an unnatural protein substrate.

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Figure 1: Mechanism of neo-substrate degradation by bifunctional degraders.


  1. Kenten, J.H. & Roberts, S.F. Controlling protein levels in eucaryotic organisms. US patent 6306663 B1 (2001).

  2. Winter, G.E. et al. Science 348, 1376–1381 (2015).

    Article  CAS  Google Scholar 

  3. Lu, J. et al. Chem. Biol. 22, 755–763 (2015).

    Article  CAS  Google Scholar 

  4. Zengerle, M., Chan, K.H. & Ciulli, A. ACS Chem. Biol. 10, 1770–1777 (2015).

    Article  CAS  Google Scholar 

  5. Sakamoto, K.M. et al. Proc. Natl. Acad. Sci. USA 98, 8554–8559 (2001).

    Article  CAS  Google Scholar 

  6. Fischer, E.S., Park, E., Eck, M.J. & Thomä, N.H. Curr. Opin. Struct. Biol. 37, 115–122 (2016).

    Article  CAS  Google Scholar 

  7. Gadd, M.S. et al. Nat. Chem. Biol. 13, 514–521 (2017).

    Article  CAS  Google Scholar 

  8. Deshaies, R.J. & Joazeiro, C.A. Annu. Rev. Biochem. 78, 399–434 (2009).

    Article  CAS  Google Scholar 

  9. Petzold, G., Fischer, E.S. & Thomä, N.H. Nature 532, 127–130 (2016).

    Article  CAS  Google Scholar 

  10. Ito, T. & Handa, H. Int. J. Hematol. 104, 293–299 (2016).

    Article  Google Scholar 

Download references

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Correspondence to Nicolas H Thomä.

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Walczak, M., Petzold, G. & Thomä, N. You can glue it too!. Nat Chem Biol 13, 452–453 (2017).

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