6XRI

MSMEG_2027 domain-swapped dimer

6XRI の概要

• エントリーDOI: 10.2210/pdb6xri/pdb
• 関連するPDBエントリー: 6WTA
• 分子名称: Uncharacterized protein (2 entities in total)
• 機能のキーワード: f420, quinone, reductase, oxidoreductase
• 由来する生物種: Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155)
• タンパク質・核酸の鎖数: 14
• 化学式量合計: 224392.48

構造登録者

Jackson, C.J.,Antoney, J.P.,Ahmed, F.H. (登録日: 2020-07-13, 公開日: 2021-07-21, 最終更新日: 2025-05-14)

主引用文献

Antoney, J.,Kainrath, S.,Dubowsky, J.G.,Ahmed, F.H.,Kang, S.W.,Mackie, E.R.R.,Granado, G.B.,Soares da Costa, T.P.,Jackson, C.J.,Janovjak, H.
A F 420 -dependent single domain chemogenetic tool for protein de-dimerization.
J.Mol.Biol., :169184-169184, 2025

PubMed Abstract: Protein-protein interactions (PPIs) mediate many fundamental cellular processes. Control of PPIs through optically or chemically responsive protein domains has had a profound impact on basic research and some clinical applications. Most chemogenetic methods induce the association, i.e., dimerization or oligomerization, of target proteins, whilst the few available dissociation approaches either break large oligomeric protein clusters or heteromeric complexes. Here, we have exploited the controlled dissociation of a homodimeric oxidoreductase from mycobacteria (MSMEG_2027) by its native cofactor, F, which is not present in mammals, as a bioorthogonal monomerization switch. Using X-ray crystallography, we found that in the absence of F MSMEG_2027 forms a unique domain-swapped dimer that occludes the cofactor binding site. Rearrangement of the N-terminal helix upon F binding results in the dissolution of the dimer. We then showed that MSMEG_2027 can be fused to proteins of interest in human cells and applied it as a tool to induce and release MAPK/ERK signalling downstream of a chimeric fibroblast growth factor receptor 1 (FGFR1) tyrosine kinase. This F-dependent chemogenetic de-homodimerization tool is stoichiometric and based on a single domain and thus represents a novel mechanism to investigate protein complexes in situ.

PubMed: 40324743
DOI: 10.1016/j.jmb.2025.169184

実験手法

X-RAY DIFFRACTION (2.37 Å)