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 2025-06-05T01:00:09Z 2025-06-05T01:00:09Z 2025-06-04 2025-09 0022-2836 https://pubs.kist.re.kr/handle/201004/152555 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) English Academic Press A F420-dependent Single Domain Chemogenetic Tool for Protein De-dimerization Article 10.1016/j.jmb.2025.169184 1 Journal of Molecular Biology, v.437, no.17 Journal of Molecular Biology 437 17 Y scie scopus 001494762800001 2-s2.0-105004933090 Biochemistry & Molecular Biology Biochemistry & Molecular Biology Article 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