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. 2021 Sep 22;599(7883):158–164. doi: 10.1038/s41586-021-03935-z

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Extended Data Fig. 14 — a. Model for Kv4 modulation by KChIP. KChIPs capture the Kv4 N- and C-termini, thereby inhibiting open state inactivation (OSI). On the other hand, KChIPs stabilize the S6 conformation and might enable synchronized movement of the four S6 gating helices, thereby accelerating closed state inactivation and recovery. b. Model for Kv4 modulation by DPP. DPPs might stabilize the conformation of Kv4 S1-S2 and facilitate S4 conformational change, including S4 sliding up and down, thereby accelerating activation, inactivation, and recovery. c. Model for Kv4 modulation in the Kv4–DPP–KChIP ternary complex. KChIPs capture the Kv4 N- and C-termini of two adjacent subunits, thereby prevent open state inactivation (OSI). As a result, Kv4 ternary complex preferentially inactivates from a closed activated state (CSI). In addition, KChIPs stabilize the S6 conformation and accelerates S6 gating. DPPs stabilize the conformation of Kv4 S1-S2 and accelerates S4 conformation change including S4 movement upon membrane voltage shift. All together additive modulations by KChIPs and DPPs confer A-type current characterized as fast activation, fast closed state inactivation, and fast recovery.