Abstract
Voltage-gated potassium channels elicit membrane hyperpolarization through voltage-sensor domains that regulate the conductive status of the pore domain. To better understand the inherent basis for the open-closed equilibrium in these channels, we undertook an atomistic scan using synthetic fluorinated derivatives of aromatic residues previously implicated in the gating of Shaker potassium channels. Here we show that stepwise dispersion of the negative electrostatic surface potential of only one site, Phe481, stabilizes the channel open state. Furthermore, these data suggest that this apparent stabilization is the consequence of the amelioration of an inherently repulsive open-state interaction between the partial negative charge on the face of Phe481 and a highly co-evolved acidic side chain, Glu395, and this interaction is potentially modulated through the Tyr485 hydroxyl. We propose that the intrinsic open-state destabilization via aromatic repulsion represents a new mechanism by which ion channels, and likely other proteins, fine-tune conformational equilibria.
| Original language | English |
|---|---|
| Journal | Nature Communications |
| Volume | 4 |
| Pages (from-to) | 1784 |
| ISSN | 2041-1723 |
| DOIs | |
| Publication status | Published - 2013 |
Keywords
- Amino Acid Sequence
- Animals
- Glutamic Acid
- Halogenation
- Ion Channel Gating
- Kinetics
- Models, Biological
- Models, Molecular
- Molecular Sequence Data
- Mutant Proteins
- Mutation
- Phenylalanine
- Potassium Channels, Voltage-Gated
- Protein Binding
- Static Electricity
- Statistics as Topic
- Surface Properties
- Xenopus laevis