Native Mass Spectrometry Analysis of Cullin RING Ubiquitin E3 Ligase Complexes in the Context of Targeted Protein Degradation.

ABSTRACT: The binding of PROTACs to their partner ubiquitin E3 ligase (E3) and a protein of interest (POI) is critical for PROTAC development and validation. Characterisation of PROTAC complexes by cryo-electron microscopy and X-ray crystallography is not always feasible, especially where species may be transient and protein structures may not resolve due to flexible domains or intrinsically disordered regions. More routine biophysical methods with broader applicability to varied samples is desirable to support the rapidly expanding targeted protein degradation field. The majority of PROTACs in development and in the clinic act through a Cullin RING E3 Ligase (CRL) of which the pentameric von Hippel-Lindau (VHL) Cullin 2 RING E3 complex (CRL2^VHL) is the foundational example. Native mass s

SUBMITTER: Sternicki LM 

PROVIDER: S-EPMC12803233 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature