A F420-dependent Single Domain Chemogenetic Tool for Protein De-dimerization
- Authors
- Antoney, James; Kainrath, Stephanie; Dubowsky, Joshua G.; Ahmed, F. Hafna; Kang, Suk Woo; Mackie, Emily R. R.; Granado, Gustavo Bracho; da Costa, Tatiana P. Soares; Jackson, Colin J.; Janovjak, Harald
- Issue Date
- 2025-09
- Publisher
- Academic Press
- Citation
- Journal of Molecular Biology, v.437, no.17
- Abstract
- Protein-protein interactions (PPIs) mediate many fu optically or chemically responsive protein domains some clinical applications. Most chemogenetic m oligomerization, of target proteins, whilst the few av gomeric protein clusters or heteromeric complexes. a homodimeric oxidoreductase from mycobacteria not present in mammals, as a bioorthogonal mon found that in the absence of F420 MSMEG_2027 f the cofactor binding site. Rearrangement of the N-t tion of the dimer. We then showed that MSMEG_20 and applied it as a tool to induce and release MAP ndamental cellular processes. Control of PPIs through has had a profound impact on basic research and ethods induce the association, i.e., dimerization or ailable dissociation approaches either break large oli-Here, we have exploited the controlled dissociation of (MSMEG_2027) by its native cofactor, F420, which is omerization switch. Using X-ray crystallography, we orms a unique domain-swapped dimer that occludes erminal helix upon F420 binding results in the dissolu-27 can be fused to proteins of interest in human cells K/ERK signalling downstream of a chimeric fibroblast growth factor receptor 1 (FGFR1) tyrosine homodimerization tool is stoichiometric and based o anism to investigate protein complexes in situ. (c) 2025 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (filipcreativecom mons.org/licenses/by/4.0)
- Keywords
- DEAZAFLAVIN-DEPENDENT NITROREDUCTASE; ISOTHERMAL TITRATION CALORIMETRY; RECEPTOR TYROSINE KINASES; FLUORESCENT PROTEIN; ACTIVATION; MODEL; SYSTEM; INTEGRATION; EXPRESSION; STRATEGY; protein-protein interaction; bioorthogonal; dimerization; receptor tyrosine kinase; oxidoreductase
- ISSN
- 0022-2836
- URI
- https://pubs.kist.re.kr/handle/201004/152555
- DOI
- 10.1016/j.jmb.2025.169184
- Appears in Collections:
- KIST Article > Others
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