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Updated: May 15, 2026

Discovering Protein Interactions and Characterizing Protein Function Using HaloTag Technology
Published on: July 12, 2014
BromoCatch: a self-labelling tag platform for protein modification and live cell imaging
Maria Rodriguez-Rios1, Conner Craigon1, Mark A Nakasone1
1Centre for Targeted Protein Degradation, School of Life Sciences, University of Dundee, Dundee, UK.
Researchers developed BromoCatch, a novel bromodomain-based self-labelling protein (SLP) platform for live-cell protein visualization and manipulation. This new tool offers enhanced multiplexing capabilities and expands applications beyond existing systems like HaloTag.
Area of Science:
- Biochemistry
- Molecular Biology
- Chemical Biology
Background:
- Live-cell protein visualization and manipulation are vital for understanding biological processes.
- Existing self-labelling protein (SLP) systems like HaloTag and SNAP-tag have limitations in multiplexing and application scope.
- Development of novel SLP platforms is needed to overcome these limitations.
Purpose of the Study:
- To introduce BromoCatch, a new bromodomain-based SLP platform.
- To engineer a robust and modular SLP system for covalent ligand engagement.
- To demonstrate the versatility and orthogonality of BromoCatch for various applications.
Main Methods:
- Structure-based design and screening of electrophilic ligands against engineered bromodomain mutants.
- Utilized differential scanning fluorimetry and mass spectrometry to identify optimal protein-ligand pairs.
- Employed NanoBRET, residence-time assays, and X-ray crystallography to characterize BromoCatch's binding and engagement.
Main Results:
- Identified an optimal BromoCatch protein-ligand pair (Brd4-BD2 mutant and MR116 ligand) with a high-resolution crystal structure.
- Demonstrated potent, irreversible cellular target engagement and orthogonality with HaloTag.
- Showcased BromoCatch's utility in creating biotinylated conjugates, PROTAC degraders, and fluorescent probes.
Conclusions:
- BromoCatch is a robust, modular, and orthogonal SLP tool for live-cell applications.
- The platform enables advanced protein labelling and targeted manipulation.
- BromoCatch significantly expands the toolkit for multiplexed imaging and functional studies in live cells.
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