Fig. 5: Extracellular inhibition of TREK-2 by Nb-Inhibitor-61. | Nature Communications

Fig. 5: Extracellular inhibition of TREK-2 by Nb-Inhibitor-61.

From: Extracellular modulation of TREK-2 activity with nanobodies provides insight into the mechanisms of K2P channel regulation

Fig. 5

A Dose-response relationships showing inhibition of TREK-2 channel activity by Nb-Inhibitor-61 (Nb61). Whole-cell TREK-2 currents were recorded at +40 mV and perfused with different concentrations of Nb67. Also shown are the effect of different mutations of K103 in Nb61. (Error bars represent mean ± S.D; n ≥ 5). B The crystal structure unit cell reveals only one Nb61 bound to TREK-2; packing interactions between the Cap domains within the crystal prevent binding to the other side. C Expanded view of the major interactions of Nb61 with the top of M3 and the M3-PH2 loop. D Alignment with TREK-2 Up-state (4BW5 in Grey) highlights displacement of M4 and PH2-M4 loop inwards towards the K2P modulator pocket. E Surface view showing obstruction of the extracellular ion exit pathway by Nb61 (in purple). K103 within the obstructed pathway is also marked (in red). F Expanded view of the ___location of K103 within the ion exit pathway. K+ ions are shown as purple spheres and the arrows indicate the direction of K+ flow through the ion exit pathway that is obstructed by K103 on CDR3 of Nb61.

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