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. 2024 May 13;147(6):2053–2068. doi: 10.1093/brain/awae078

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© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

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Interaction between RGNEF/NF242 and TDP-43. (A) Representative SPR sensorgrams showing the interaction between His-GST-TDP-43^wt (analyte) and His-MBP-RGNEF^1–275 (ligand) at different concentrations of His-GST-TDP-43^wt. K_D = 1.78 ± 0.49 μM (n = 4). (B) NanoBiT experiment showing interaction between TDP-43^wt (structure detailed) and NF242 (NF) (n = 3; NC = negative control). (C) NanoBiT experiment showing interaction between TDP-43^1–366 (structure detailed) and NF242 (NF) (n = 3; NC = negative control). (D) NanoBiT experiment showing interaction between TDP-43^1–274 (structure detailed) and NF242 (NF) (n = 3; NC = negative control). (E) NanoBiT experiment showing an absence of interaction between TDP-43^ΔRRM1–2 (structure detailed) and NF242 (NF) (n = 3; NC = negative control). (F) Representative SPR sensorgrams showing the interaction between His-TDP-43^1–269 (analyte) and His-MBP-RGNEF^1–275 (ligand) at different concentrations of His-TDP-43^1–269. K_D = 4.11 ± 1.33 μM (n = 3). (G) Representative SPR sensorgrams demonstrating the absence of interaction between His-TDP-43^1–102 (analyte) and His-MBP-RGNEF^1–275 (ligand) at different concentrations of His-TDP-43^1–102 (n = 3). (H) NanoBiT experiment showing interaction between TDP-43^ΔRRM1 (structure detailed) and NF242 (NF) (n = 3; NC = negative control). (I) NanoBiT experiment showing the lack of interaction between TDP-43^ΔRRM2 (structure detailed) and NF242 (NF) (n = 3; NC = negative control). (J) Representative SPR sensorgrams demonstrating the interaction between His-RRM1 (analyte) and His-MBP-RGNEF^1–275 (ligand) at different concentrations of His-RRM1(n = 4). (K) Representative SPR sensorgrams demonstrating weak interaction (low signal intensity) between His-RRM2 (analyte) and His-MBP-RGNEF^1–275 (ligand) at different concentrations of His-RRM2 (n = 4). (L) NanoBiT experiment showing interaction between TDP-43^1–192 (structure detailed) and NF242 (NF) (n = 3; NC = negative control). RRM = RNA recognition motif; SPR = surface plasmon resonance spectroscopy.