Alessio Ciulli

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

This study uses native mass spectrometry to characterize CRL2VHL complexes and their interactions with PROTACs and POIs, revealing key multiprotein assemblies involved in targeted protein degradation.

LRRC58 defines an E3 ubiquitin ligase complex sensitive to cysteine abundance

The paper identifies LRRC58 as a substrate adaptor in a Cul2 E3 ligase complex that regulates CDO1 degradation in response to cysteine availability, preventing ferroptosis and neurodevelopmental defects.

Photocrosslinking Activity-Based Probes to Capture the Dynamics of Ubiquitin RING E3 Ligase Interactions

The paper develops a photocrosslinking activity-based probe to study interactions between ubiquitin and RING E3 ligases, confirming existing structures and evaluating new models.

Scalable insect cell expression and purification screening applied to CRL4-DCAF substrate receptors

The paper describes a high-throughput screening method for expressing and purifying DCAF proteins in insect cells, identifying 8 previously unexpressed DCAFs as promising candidates for further study.

Medulloblastoma-Associated KBTBD4 Mutations Disrupt PP2A-A Orphan Quality Control

This study identifies PP2A-A as a target of CRL3KBTBD4, showing that KBTBD4 mutations disrupt PP2A quality control and contribute to medulloblastoma by altering phospho-dependent signaling.

High-throughput diversification of protein-ligand surfaces to discover chemical inducers of proximity

This study uses high-throughput chemistry to discover chemical inducers of proximity by modifying pre-existing ligands and screening for degrader activity.

Tuning the open-close equilibrium of Cereblon with small molecules influences protein degradation

This study identifies CRBN binders that induce or fail to induce CRBN closure, showing that closure is critical for degrader activity.

Linker-rigidified VHL homodimerizers convert degraders into stabilizers of non-ubiquitinable ternary complexes

Induced ubiquitination of the partially disordered Estrogen Receptor alpha protein via a 14-3-3-directed molecular glue-based PROTAC design

This paper develops a molecular glue-based PROTAC (MGPROTACs) to ubiquitinate the 14-3-3/Estrogen Receptor complex, demonstrating cooperative complex formation and selective ubiquitination through linker design.

Selective degradation of BRD9 by a DCAF16-recruiting targeted glue: mode of action elucidation and in vivo proof of concept

The paper identifies a potent BRD9 degrader, AMPTX-1, which selectively recruits BRD9 to DCAF16, leading to its degradation in vivo.

Frustration in the Protein-Protein interface Plays a Central Role in the Cooperativity of PROTAC Ternary Complexes

This study shows that frustration in the SMARCA2-VHL protein-protein interface correlates with PROTAC cooperativity, offering a framework for structure-based PROTAC design.

Dual E3 ligase recruitment by monovalent degraders enables redundant and tuneable degradation of SMARCA2/4

This study shows that a monovalent MGD can recruit two E3 ligases redundantly to degrade SMARCA2/4, with tunable ligase preference through chemical and genetic modifications.

A method for the detection and enrichment of endogenous cereblon substrates

This paper introduces a method called cerebody to detect and enrich endogenous cereblon substrates by targeting C-terminal cyclic imide modifications.

BromoCatch: a self-labelling tag platform for protein analysis and live cell imaging

BromoCatch is a new self-labelling protein tag platform that enables rapid, specific, and stable protein labelling in live cells through covalent ligand engagement.

Charting functional E3 ligase hotspots and resistance mechanisms to small-molecule degraders

The paper identifies functional E3 ligase hotspots and resistance mechanisms to small-molecule degraders using haploid genetics and deep mutational scanning.