A deep dive into degrader-induced protein-protein interfaces

Pius Galli; Carlos Pla-Prats; Nicolas H Thomä

doi:10.1016/j.tips.2023.02.001

A deep dive into degrader-induced protein-protein interfaces

Trends Pharmacol Sci. 2023 Apr;44(4):196-198. doi: 10.1016/j.tips.2023.02.001. Epub 2023 Feb 22.

Authors

Pius Galli¹, Carlos Pla-Prats¹, Nicolas H Thomä²

Affiliations

¹ Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland; University of Basel, Petersplatz 1, 4051 Basel, Switzerland.
² Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland. Electronic address: Nicolas.Thoma@fmi.ch.

PMID: 36828760
DOI: 10.1016/j.tips.2023.02.001

Abstract

Targeted protein degradation (TPD) relies on a comprehensive understanding of interfaces between hijacked E3 ligases and their substrates. In vitro techniques often do not capture the interaction dynamics. Recently, Hanzl et al. introduced deep mutational scanning (DMS) in combination with structural and biochemical approaches to identify residues crucial for degrader activity.

Keywords: degrader resistance; saturation mutagenesis; targeted protein degradation; ubiquitin ligase.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Humans
Mutation
Proteins* / metabolism
Proteolysis
Ubiquitin-Protein Ligases* / chemistry
Ubiquitin-Protein Ligases* / genetics
Ubiquitin-Protein Ligases* / metabolism

Substances

Proteins
Ubiquitin-Protein Ligases