title: Inter-subunit interactions across the upper voltage sensing-pore domain interface contribute to the concerted pore opening transition of Kv channels.
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.
authors: Department of Life Sciences and the Zlotowski Center for Neurosciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
authors: Tzilhav
authors: T
authors: Shem-Ad
authors: Orr
authors: O
authors: Irit
authors: Ofer
authors: O
authors: Yifrach
mesh_terms: D000818:Animals; D015640:Ion Channel Gating / Q000502:physiology*; D055503:Protein Multimerization / Q000502:physiology*; D017434:Protein Structure, Tertiary; D051637:Shaker Superfamily of Potassium Channels / Q000235:genetics / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D051637:Shaker Superfamily of Potassium Channels