s1 constrains s4 in the voltage sensor domain of kv7.1 k+ channelss1限制电压传感器领域的s4 kv7.1 k +通道.pdfVIP

S1 Constrains S4 in the Voltage Sensor Domain of Kv7.1 K+ Channels 1. 1. 1. 1 1 1 Yoni Haitin , Ilanit Yisharel , Eti Malka , Liora Shamgar , Hella Schottelndreier , Asher Peretz , Yoav 2 1 Paas , Bernard Attali * 1 Department of Physiology and Pharmacology, Sackler Medical School, Tel Aviv University, Tel Aviv, Israel, 2 The Mina and Everard Goodman Faculty of Life Sciences Bar- Ilan University, Ramat-Gan, Israel Abstract Voltage-gated K+ channels comprise a central pore enclosed by four voltage-sensing domains (VSDs). While movement of the S4 helix is known to couple to channel gate opening and closing, the nature of S4 motion is unclear. Here, we substituted S4 residues of Kv7.1 channels by cysteine and recorded whole-cell mutant channel currents in Xenopus oocytes using the two-electrode voltage-clamp technique. In the closed state, disulfide and metal bridges constrain residue S225 (S4) nearby C136 (S1) within the same VSD. In the open state, two neighboring I227 (S4) are constrained at proximity while residue R228 (S4) is confined close to C136 (S1) of an adjacent VSD. Structural modeling predicts that in the closed to open ˚ transition, an axial rotation (,190u) and outward translation of S4 (,12 A) is accompanied by VSD rocking. This large sensor motion changes the intra-VSD S1–S4 interaction to an inter-VSD S1–S4 interaction. These constraints provide a ground for cooperative subunit interactions and suggest a key role of the S1 segment in steering S4 motion during Kv7.1 gating. Citation: Haitin Y, Yisharel I, Malka E, Shamgar L, Schottelndreier H, et al. (2008) S1 Co