A F420-dependent Single Domain Chemogenetic Tool for Protein De-dimerization

Authors
Antoney, JamesKainrath, StephanieDubowsky, Joshua G.Ahmed, F. HafnaKang, Suk WooMackie, Emily R. R.Granado, Gustavo Brachoda Costa, Tatiana P. SoaresJackson, 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
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KIST Article > Others
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