Extent of voltage sensor movement during gating of Shaker K+ channels

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 angstrom transmembrane paddle-type movement or a near-zero A vertical transporter-type model. Rather, our measurements demonstrate a moderate S4 displacement of 10 +/- 5 angstrom, with a vertical component of 5 +/- 2 angstrom. The S3 segment moves 2 +/- 1 angstrom in the opposite direction and is therefore not moving as an S3-S4 rigid body.