Deprotonation of arginines in S4 is involved in NaChBac gating

AUTHORS Tzur Paldi

ADMIN(S) Tzur Paldi

ABSTRACT Voltage-gated ion channels participate in cell excitability by enabling selective ion flux in response to changes in the membrane potential. The channel senses voltage across the membrane via a voltage-sensing module composed of four membrane-spanning helices (S1-S4). A stretch of positively charged arginines in the fourth transmembrane segment (S4) that traverses the membrane’s electric field, is the principal sensing component of the module. Yet, the driving forces behind S4 movement are not fully understood. The prevailing helical-screw model, which describes the movement of S4 along its axis, suggests that salt bridges between positively-charged residues on S4 and negatively-charged residues on S1-S3, alternately break and reform in the course of S4 movement. However, the estimated energy needed to separate the charges in a low dielectric cavity, is incompatible with experimental data (Green ME, J Theor Biol 193:475-483, 1998). Here, it is shown that extracellular titration of the three outermost arginines on S4 stabilizes the bacterial voltage-gated sodium channel (NaChBac) at different states, and enhances the coupling of the outermost arginine on S4, with E43 on S1. It is suggested that salt bridges that stabilize S4 are impaired by arginine deprotonation during voltage-sensing module activity. It is also shown that acid-induced channel blocking is strongly affected by arginine substitutions at S4. The electrostatic interactions of these arginines with acidic residues, exemplified by a structural model of NaChBac, suggests that extracellular acidification induces the retraction of S4, thereby enhancing channel inactivation by reclosure of the channel’s activation gate.

Ness Technologies Systems Group

The Journal of membrane biology, doi: 10.1007/s00232-012-9430-x

KEY WORDS Electrostatic interactions, Helical screw, pKa shift, Ion channels, Voltage dependent, Voltage gated, Voltage sensor domain, Voltage sensing

SPAPER ID 4046

Currently the author holds the copyright for this article. It was formerly accepted and published (online; http://sdrv.ms/PEu7sG) at the J MEMBRANE BIOL before it was pulled out by the author due to violation of the author's copyrighs. You can use it or any part of it as long as you indicate its source: Paldi T (2012) Deprotonation of arginines in S4 is involved in NaChBac gating. http://sdrv.ms/13hN4Vm