The S4 segment of the voltage-gated proton channel VSOP inserts into the membrane and retains channel function even when truncated downstream of R2, providing insights into voltage sensing mechanisms.
Truncation data refine VSOP voltage-sensing models; leaves open translation to cardiac proton channel function.
The voltage-sensor domain (VSD) is the key module for voltage sensing of transmembrane proteins. Recently, voltage-sensor only protein (VSOP) that contains a single VSD but no pore domain was discovered and functions as the voltage-gated proton channel. The fourth transmembrane segment (S4) of VSOP contains three arginines (R1, R2, R3). We found that VSOP truncated just downstream of R2 retains most channel properties. Two assays, PEGylation-protection assay and membrane insertion assay, showed that S4 inserts into the membrane, even if it is truncated between R2 and R3. These findings provide important clues to the molecular mechanism of voltage-gated proton channel.
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Kurokawa et al. (2011) studied this question.
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