2LE7

Solution nmr structure of the S4S5 linker of herg potassium channel

Summary for 2LE7

• Entry DOI: 10.2210/pdb2le7/pdb
• NMR Information: BMRB: 17699
• Descriptor: Potassium voltage-gated channel subfamily H member 2 (1 entity in total)
• Functional Keywords: herg, s4s5, voltage-gated potassium channel, membrane protein, transport protein
• Biological source: Homo sapiens (Human)
• Cellular location: Membrane; Multi-pass membrane protein: Q12809
• Total number of polymer chains: 1
• Total formula weight: 2330.73

Authors

Ng, C.A.,Kuchel, P.W.,Vandenberg, J.I. (deposition date: 2011-06-13, release date: 2012-04-25, Last modification date: 2024-05-15)

Primary citation

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

Experimental method

SOLUTION NMR