Inter-subunit interactions across the upper voltage sensing-pore domain interface contribute to the concerted pore opening transition of Kv channels

PLoS One. 2013 Dec 10;8(12):e82253. doi: 10.1371/journal.pone.0082253. eCollection 2013.

Abstract

The tight electro-mechanical coupling between the voltage-sensing and pore domains of Kv channels lies at the heart of their fundamental roles in electrical signaling. Structural data have identified two voltage sensor pore inter-domain interaction surfaces, thus providing a framework to explain the molecular basis for the tight coupling of these domains. While the contribution of the intra-subunit lower domain interface to the electro-mechanical coupling that underlies channel opening is relatively well understood, the contribution of the inter-subunit upper interface to channel gating is not yet clear. Relying on energy perturbation and thermodynamic coupling analyses of tandem-dimeric Shaker Kv channels, we show that mutation of upper interface residues from both sides of the voltage sensor-pore domain interface stabilizes the closed channel state. These mutations, however, do not affect slow inactivation gating. We, moreover, find that upper interface residues form a network of state-dependent interactions that stabilize the open channel state. Finally, we note that the observed residue interaction network does not change during slow inactivation gating. The upper voltage sensing-pore interaction surface thus only undergoes conformational rearrangements during channel activation gating. We suggest that inter-subunit interactions across the upper domain interface mediate allosteric communication between channel subunits that contributes to the concerted nature of the late pore opening transition of Kv channels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ion Channel Gating / physiology*
  • Protein Multimerization / physiology*
  • Protein Structure, Tertiary
  • Shaker Superfamily of Potassium Channels / genetics
  • Shaker Superfamily of Potassium Channels / metabolism*
  • Thermodynamics

Substances

  • Shaker Superfamily of Potassium Channels

Associated data

  • PDB/2R9R

Grants and funding

The study was funded by a Israel Science Foundation grant # 488/12. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.