Targeted protein degradation

You can glue it too!

Article metrics

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.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

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

References

  1. 1

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

  2. 2

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

  3. 3

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

  4. 4

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

  5. 5

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

  6. 6

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

  7. 7

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

  8. 8

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

  9. 9

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

  10. 10

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

Download references

Author information

Correspondence to Nicolas H Thomä.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Walczak, M., Petzold, G. & Thomä, N. You can glue it too!. Nat Chem Biol 13, 452–453 (2017) doi:10.1038/nchembio.2355

Download citation

Further reading