Fig. 6: Engineering of a high-affinity biparatropic inhibitory nanobody. | Nature Communications

Fig. 6: Engineering of a high-affinity biparatropic inhibitory nanobody.

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

Fig. 6

A Dose-response relationships showing inhibition of TREK-2 channel activity by the divalent linked Nb-Inhibitor-6158 (Nb61). Whole-cell TREK-2 currents were recorded at +40 mV and perfused with different concentrations Nb6158. Consistent with its markedly increased affinity, this linked nanobody exhibits a marked increase in its inhibitory efficacy compared to Nb61 alone. (Error bars represent mean ± S.D; n ≥ 5) B A 7.4 Å resolution CryoEM structure of TREK-2 in complex with Nb6158 shows two copies of Nb61 bound, one to each side of the Cap domain. An expanded view of their relative position is shown on the right. This indicates that, in addition to any allosteric effects, Nb61 is capable of interacting with TREK-2 on both sides of the Cap domain to obstruct K+ permeation from both extracellular ion exit pathways.

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