Voltage-driven activation of Kv channels results from conformational changes of four voltage sensor domains (VSDs) that surround the K+ selective pore domain. How the VSD helices rearrange during gating is an area of active research. Luminescence resonance energy transfer (LRET) is a powerful spectroscopic ruler uniquely suitable for addressing the conformational trajectory of these helices. Using a geometric analysis of numerous LRET measurements, we were able to estimate LRET probe positions relative to existing structural models. The experimental movement of helix S4 does not support a large 15-20 Å transmembrane "paddle-type" movement or a near-zero Å vertical "transporter-type" model. Rather, our measurements demonstrate a moderate S4 displacement of 10 ± 5 Å, with a vertical component of 5 ± 2 Å. The S3 segment moves 2 ± 1 Å in the opposite direction and is therefore not moving as an S3-S4 rigid body.
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