2LE7

Solution nmr structure of the S4S5 linker of herg potassium channel

2LE7 の概要

• エントリーDOI: 10.2210/pdb2le7/pdb
• NMR情報: BMRB: 17699
• 分子名称: Potassium voltage-gated channel subfamily H member 2 (1 entity in total)
• 機能のキーワード: herg, s4s5, voltage-gated potassium channel, membrane protein, transport protein
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Membrane; Multi-pass membrane protein: Q12809
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 2330.73

構造登録者

Ng, C.A.,Kuchel, P.W.,Vandenberg, J.I. (登録日: 2011-06-13, 公開日: 2012-04-25, 最終更新日: 2024-05-15)

主引用文献

Ng, C.A.,Perry, M.D.,Tan, P.S.,Hill, A.P.,Kuchel, P.W.,Vandenberg, J.I.
The S4-S5 linker acts as a signal integrator for HERG K+ channel activation and deactivation gating
Plos One, 7:e31640-e31640, 2012

PubMed Abstract: Human ether-à-go-go-related gene (hERG) K(+) channels have unusual gating kinetics. Characterised by slow activation/deactivation but rapid inactivation/recovery from inactivation, the unique gating kinetics underlie the central role hERG channels play in cardiac repolarisation. The slow activation and deactivation kinetics are regulated in part by the S4-S5 linker, which couples movement of the voltage sensor domain to opening of the activation gate at the distal end of the inner helix of the pore domain. It has also been suggested that cytosolic domains may interact with the S4-S5 linker to regulate activation and deactivation kinetics. Here, we show that the solution structure of a peptide corresponding to the S4-S5 linker of hERG contains an amphipathic helix. The effects of mutations at the majority of residues in the S4-S5 linker of hERG were consistent with the previously identified role in coupling voltage sensor movement to the activation gate. However, mutations to Ser543, Tyr545, Gly546 and Ala548 had more complex phenotypes indicating that these residues are involved in additional interactions. We propose a model in which the S4-S5 linker, in addition to coupling VSD movement to the activation gate, also contributes to interactions that stabilise the closed state and a separate set of interactions that stabilise the open state. The S4-S5 linker therefore acts as a signal integrator and plays a crucial role in the slow deactivation kinetics of the channel.

PubMed: 22359612
DOI: 10.1371/journal.pone.0031640

実験手法

SOLUTION NMR