The Intrinsic Flexibility of the Kv Voltage Sensor and its Implications for Channel Gating.

@article{citeulike:449865, abstract = {Analysis of the crystal structures of the intact voltage sensitive potassium channel KvAP (from Aeropyrum pernix) and Kv1.2 (from rat brain), along with the isolated voltage sensor (VS) domain from KvAP, raises the question of the exact nature of the voltage-sensing conformational change that triggers activation of Kv and related voltage gated channels. Molecular dynamics simulations of the isolated VS of KvAP in a detergent micelle environment at two different temperatures (300 K and 368 K) have been used to probe the intrinsic flexibility of this domain on a tens-of-nanoseconds timescale. The VS contains a positively charged (S4) helix which is packed against a more hydrophobic S3 helix. The simulations at elevated temperature reveal an intrinsic flexibility/conformational instability of the S3a region (i.e. the C-terminus of the S3 helix). It is also evident that the S4 helix undergoes hinge bending and swivelling about its central I130 residue. The conformational instability of the S3a region facilitates the motion of the N-terminal segment of S4 (i.e. S4a). These simulations thus support a gating model in which, in response to depolarization, an S3b-S4a 'paddle' may move relative to the rest of the VS domain. The flexible S3a region may in turn act to help restore the paddle to its initial conformation upon re-polarization.}, address = {Univ of Oxford.}, author = {Sands, Zara A. A. and Grottesi, Alessandro and Sansom, Mark S. S. }, citeulike-article-id = {449865}, doi = {http://dx.doi.org/10.1529/biophysj.105.072199}, issn = {0006-3495}, journal = {Biophys J}, keywords = {kv12, kvap, md, simulations, voltage-sensor}, month = {December}, posted-at = {2005-12-26 01:57:41}, priority = {2}, title = {The Intrinsic Flexibility of the Kv Voltage Sensor and its Implications for Channel Gating.}, url = {http://dx.doi.org/10.1529/biophysj.105.072199}, year = {2005} }

TY - JOUR ID - citeulike:449865 L3 - citeulike-article-id:449865 N2 - Analysis of the crystal structures of the intact voltage sensitive potassium channel KvAP (from Aeropyrum pernix) and Kv1.2 (from rat brain), along with the isolated voltage sensor (VS) domain from KvAP, raises the question of the exact nature of the voltage-sensing conformational change that triggers activation of Kv and related voltage gated channels. Molecular dynamics simulations of the isolated VS of KvAP in a detergent micelle environment at two different temperatures (300 K and 368 K) have been used to probe the intrinsic flexibility of this domain on a tens-of-nanoseconds timescale. The VS contains a positively charged (S4) helix which is packed against a more hydrophobic S3 helix. The simulations at elevated temperature reveal an intrinsic flexibility/conformational instability of the S3a region (i.e. the C-terminus of the S3 helix). It is also evident that the S4 helix undergoes hinge bending and swivelling about its central I130 residue. The conformational instability of the S3a region facilitates the motion of the N-terminal segment of S4 (i.e. S4a). These simulations thus support a gating model in which, in response to depolarization, an S3b-S4a 'paddle' may move relative to the rest of the VS domain. The flexible S3a region may in turn act to help restore the paddle to its initial conformation upon re-polarization. JF - Biophys J SN - 0006-3495 AD - Univ of Oxford. TI - The Intrinsic Flexibility of the Kv Voltage Sensor and its Implications for Channel Gating. KW - kv12 KW - kvap KW - md KW - simulations KW - voltage-sensor AU - Sands, Zara AU - Grottesi, Alessandro AU - Sansom, Mark PY - 2005/12/02/ UR - http://dx.doi.org/10.1529/biophysj.105.072199 ER -