CATCHFIRE: the reversible, self-reporting protein dimerizer

CATCHFIRE: a self-reporting, reversible protein dimerizer

CATCHFIRE, Chemically Assisted Tethering of CHimera by Fluorogenic-Induced Recognition, is a fluorogenic chemically induced dimerization (CID) technology. In a single step, one small molecule brings two chosen proteins together and makes their new assembly fluorescent, so you can trigger a protein interaction and watch it happen at the same moment. Introduced in Nature Methods in 2023 by Prof. Arnaud Gautier and Dr. Franck Perez, co-founders of The Twinkle Factory, CATCHFIRE is the first self-reporting, reversible protein dimerizer: it turns the control of protein proximity into a directly observable, switchable event.

The CATCHFIRE principle: a fluorogenic match glue recruits FIREmate- and FIREtag-fused proteins into a reversible, fluorescent ternary assembly (left), using dyes that span green to far-red (right).

How CATCHFIRE works

Two proteins of interest are genetically fused to two small partner domains, FIREmate and FIREtag (the latter just 10 amino acids). A cognate fluorogenic “molecular glue” of the match family then bridges the two domains, and the ternary assembly lights up, the signal of ^match550, for instance, rises about 100-fold on binding. Because the glue is added rather than genetically encoded, the interaction is fully reversible: wash the match out and the two proteins part again.

• Self-reporting, the glue is the fluorophore, so recruitment is read out directly, with no separate reporter to build.
• Multicolour, ^match540 (green), ^match600 (orange) and ^match715 (far-red) glues span the spectrum for multiplexed experiments.
• Actuation-only mode, ^matchDark, a non-fluorescent glue, drives proximity without adding a fluorescent signal when you don’t want one.
• Tiny footprint, the 10-aa FIREtag minimises perturbation of the tagged protein.

How CATCHFIRE compares with other proximity tools

Controlling protein proximity is a cornerstone of modern cell biology, and CATCHFIRE fills a niche older tools do not:

• vs. classical chemical dimerizers (rapamycin FKBP–FRB, gibberellin, abscisic acid): these induce proximity but are not self-reporting, you must add a separate fluorescent tag to see the event, and are often slow or poorly reversible; CATCHFIRE reports and reverses on its own.
• vs. optogenetic dimerizers (CRY2–CIB1, iLID, Magnets): light control is fast, but it needs illumination hardware, can be phototoxic, and competes with the imaging channels; CATCHFIRE uses a simple, inexpensive small-molecule glue instead.
• vs. split fluorescent reporters (splitFAST, split-GFP): those report an interaction but cannot induce one, CATCHFIRE does both.

What you can do with CATCHFIRE

A sampling of CATCHFIRE applications, membrane and organelle recruitment, transport, translocation and biosensing (from Wang et al., Nat. Methods 2023).

Because a single reagent both actuates and reports proximity, CATCHFIRE has quickly found a broad range of uses:

• Targeted recruitment, deliver a protein to the ER, Golgi, plasma or mitochondrial membrane on demand.
• Organelle positioning and transport, couple organelles such as lysosomes to motor proteins and move them along microtubules.
• Inducible translocation, drive a protein into the nucleus, then release it by washout.
• Biosensing, report enzymatic events such as caspase-3 activity during apoptosis.
• Light control, a caged FIREtag adds photo-activation for spatial precision.
• Drug discovery, high-throughput screening of protein–protein interactions and cellular pathways.

A fast-growing toolbox

Since its 2023 debut, CATCHFIRE has moved quickly from a method to a platform. It shares its fluorogen chemistry with the FAST family, the match glues are HBR-derived, like the TFFluorogens, which is why the two technologies interoperate so naturally. The surrounding literature is already expanding from foundational cell-biology applications toward high-throughput screening in bacteria, organelle-contact-site studies, and near-infrared variants, marking CATCHFIRE as one of the most versatile entries in the chemogenetics toolbox.

Get started with CATCHFIRE using our match molecular glues and kits.

Explore the peer-reviewed evidence

CATCHFIRE and its applications are documented in a growing body of peer-reviewed work. Browse the searchable database below, filter by year or publication type, with a direct link to every paper.